Nagoya University Graduate School of Medicine.

Nagoya University Graduate School of Medicine.

Nagoya University Graduate School of Medicine.
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We are a cancer and fibrosis biology research group at Nagoya University Graduate School of Medicine, Japan. We have been interested in understanding the underlying mechanisms that contribute to the progression of cancer as well as fibrotic diseases. Our approaches have been based on the functional analysis of the genes or proteins of our interest along with histological and pathological investigations of human tissue samples. Our mission also includes fostering qualified specialists for pathological diagnosis who contribute to public health. For training pathology residents, we are collaborating with our colleagues at Nagoya University Hospital and its affiliated hospitals in the Chubu region of Japan. Another mission of our lab is to foster pathologists who can come up with their own research questions or niches based on their observations, background knowledge, and interests.
Our research interests cover the fields of cancer, fibrosis, and developmental biology, with a specific focus on the following research areas:

Reserch

Molecular mechanisms that underlie development and diseases that are regulated by the Akt substrate Girdin along with its family of proteins and the GPI-anchored membrane protein CD109

Our interests focus on the functions of Girdin (reviewed in Wang et al., Pathol Int, 2016) and CD109 (reviewed in Mii et al., Pathol Int, 2019) that we previously identified as the downstream effectors of the Ret signaling pathway.

Girdin, which is also known as Gα-interacting vesicle-associated protein (GIV), is an actin-binding and hub protein with many interacting proteins, and is involved in cell migration, polarization, cargo-selective endocytosis, and metabolism (Fig 1; Dev Cell, 2005; Cancer Res, 2008; Nat Cell Biol, 2008, Neuron, 2009; Oncogene, 2012; EMBO J, 2014; Cancer Res, 2015; PLoS Biol, 2018). In addition, the results of our studies on Girdin-deficient and mutant mice and human tissue samples have suggested that it is an essential regulator of collective migration and invasion of neuroblasts in the brain and cancer cells, respectively (J Neurosci, 2011; Cancer Sic, 2018, and others). We also identified that DISC1, which is encoded by a schizophrenia susceptibility gene, interacts with Girdin, and the DISC1-Girdin complex regulates the migration and positioning of newly generated neuroblasts in the hippocampus (Neuron, 2009; J Neurosci, 2011). The analysis of Daple, which is a member of the Girdin family of proteins, has also been the scope of research in our laboratory (Nat Commun, 2012; Cell Rep, 2014).

CD109 is a GPI-anchored membrane protein, which is expressed in the basal cells of the skin as well as in the myoepithelial and endothelial cells in normal tissues. It is highly overexpressed in many types of cancer cells, in which it binds to the TGF-β receptors and matrix proteins to regulate intracellular signals (Pathol Int, 2008; Oncogene, 2010; Am J Pathol, 2012; PLoS One, 2014; Oncotarget, 2016). CD109 is also highly expressed in the brain tumor stem cells (BTSCs) of gliomas and is essential for the maintenance of stemness of BTSCs (J Pathol, 2017). Our recent observation indicated that CD109 is a marker of invasive cancer cells in human lung adenocarcinoma, wherein it regulates the activation of the latent form of TGF-β in the tumor stroma (Fig 2). Owing to these findings, CD109 is one of the molecular targets for developing new anticancer therapeutics and has attracted increasing attention in the pharmaceutical sectors.

We will continue to delve into the molecular functions of these proteins and their family of proteins and reveal their involvement in the physiology of multiple tissues and the pathology of human diseases.

Fig. 1

Structure of Girdin and its interacting proteins

Fig. 2

CD109 expression in the invasive lesion (left) of human lung adenocarcinoma
Stromal biology: Understanding cancer and fibrosis biology based on the heterogeneity of stromal components

Cancer stroma comprises multiple components, including cancer-associated fibroblasts (CAFs), tumor vessels, immune cells, and the extracellular matrix. CAF proliferation is particularly prominent in devastating cancers such as pancreatic cancer. Fibroblast proliferation and alterations in its phenotype are also major causes of decline in organ functions that are associated with aging, chronic inflammation, and tissue wound and repair. Recent evidence suggests that in the case of cancer and fibrotic diseases, the stroma contains heterogeneous populations of fibroblasts (reviewed in Kobayashi et al., Nat Rev Gastroenterol Hepatol, 2019). We recently identified a GPI-anchored membrane protein, Meflin, that is a marker protein of cancer-restraining CAFs (rCAFs) and fibroblasts that inhibit fibrosis. Meflin plays a suppressive role in the progression of pancreatic cancer (Fig 3; Cancer Res, 2019; reviewed in Miyai et al., Cancer Sci, 2020) and is essential for tissue repair after acute myocardial infarction (Fig 4; Circ Res, 2019). Interestingly, induction of heart failure in Meflin-deficient mice resulted in the development of heart failure with preserved ejection fraction (HFpEF), the prevalence of which has shown an increase in the clinic recently. HFpEF is characterized by the stiffening of the heart tissue and diastolic dysfunction (Circ Res, 2019). Our next goal is to continue analyzing the significance of fibroblast heterogeneity in various human diseases by focusing on Meflin and other fibroblast markers.

Fig. 3

In situ hybridization data showing Meflin-positive rCAFs and α-SMA-positive CAFs in human pancreatic cancer

Fig. 4

Expression of Meflin in fibroblasts in cardiac tissue after myocardial infarction that is revealed by a Meflin reporter mouse (Meflin-CreERT2; Rosa26-LSL-tdTomato).
Biology of fibroblasts and mechanopathology

Meflin was originally identified as a marker of mesenchymal stem/stromal cells (MSCs) (Sci Rep, 2016). Notably, its expression is limited to undifferentiated MSCs, but is absent in differentiated MSC lineages such as osteocytes, chondrocytes, adipocytes and muscle cells, and this clearly differentiates it from other conventional MSC markers such as CD90, CD105, CD73, and CD44. As described above, Meflin is also expressed in a fibroblast subset that is located in the perivascular areas in multiple tissue types. Although fibroblasts are well known as an essential architectural component that maintains the structure of every organ and tissue, results of various recent studies revealed that some of them function as niches for tissue stem cells and are actively involved in the physiological functions of multiple organs. However, in disease conditions, the changes in the fibroblast phenotype are accompanied by the production of the extracellular matrix, which results in the stiffening of the tissues. Importantly, the mechanical stress induced by this stiff environment further alters fibroblast function along with its gene expression. Results of our recent investigation on the gene expression profile of fibroblasts indicated that the nature of fibroblasts is not completely understood yet and is much more complicated than expected. Therefore, in future, our aim is to address the question “what are fibroblasts?” based on the analysis of the markers of MSCs and fibroblasts. Another scope of our lab will be understanding the mechanisms of human diseases from a viewpoint that the mechanical stress experienced by cells in the stiff tissues is crucial for changes in cell functions, which is known as mechanopathology.

Group members

Faculty

Atsushi Enomoto, Professor
Shinji Mii, Associate Professor / Lecturer
Yukihiro Shiraki, Assistant Professor

Professor Emeritus

Masahide Takahashi (Fujita Health University)

Research fellows and PhD students

Nobutoshi Esaki, Research Fellow
Hiroki Kobayashi, Graduate Student (Joint Degree Program, Adelaide University)
Chen Chen, Graduate Student
Ryosuke Ichihara, Graduate Student (Pathology resident)
Natsumi Mori, Graduate Student (Pathology resident)
Ryota Ando, Graduate Student
Akihiro Sakai, Graduate Student
Kotaro Matsumoto, Undergraduate Student
Toshiyuki Sato, Research fellow at National Institute for Basic Biology
Tetsuro Taki, Graduate Student
Kazuyuki Akane, Visiting Researcher

Research collaborators and PhD students affiliated to other departments

Akitoshi Hara (Cardiology, Assistant Professor)
Yasuyuki Mizutani (Gastroenterology and Hapatology, Assistant Professor)
Yuki Miyai (Clinical Oncology and Chemotherapy, Clinical Fellow)
Eiji Nakamichi (Dental Surgery, Clinical Fellow)
Tadashi Iida (Gastroenterology and Hapatology, Assistant Professor)
Takayuki Owaki (Urology, Graduate Student)
Toshikazu Ishihara (Cardiology, Graduate Student)
Keita Nakanishi (Thoracic Surgery, Graduate Student)

Technical support staff

Kozo Uchiyama
Yasuko Sobue

Secretary

Kayoko Endo

Publications

  • Kozawa K, Sekai M, Ohba K, Ito S, Sako H, Maruyama T, Kakeno M, Shirai T, Kuromiya K, Kamasaki T, Kohashi K, Tanaka S, Ishikawa S, Sato N, Asano S, Suzuki H, Tanimura N, Mukai Y, Gotoh N, Tanino M, Tanaka S, Natsuga K, Soga T, Nakamura T, Yabuta Y, Saitou M, Ito T, Matsuura K, Tsunoda M, Kikumori T, Iida T, Mizutani Y, Miyai Y, Kaibuchi K, Enomoto A, Fujita Y.
    The CD44/COL17A1 pathway promotes the formation of multilayered, transformed epithelia
    Curr Biol. 2021 May 28;S0960-9822(21)00625-4. doi: 10.1016/j.cub.2021.04.078.
  • Nakahara Y, Hashimoto N, Sakamoto K, Enomoto A, Adams TS, Yokoi T, Omote N, Poli S, Ando A, Wakahara K, Suzuki A, Inoue M, Hara A, Mizutani Y, Imaizumi K, Kawabe T, Rosas IO, Takahashi M, Kaminski N, Hasegawa Y.
    Fibroblasts positive for meflin have anti-fibrotic property in pulmonary fibrosis.
    Eur Respir J. 2021 May 28:2003397. doi: 10.1183/13993003.03397-2020.
  • Kawabata T, Suga H, Takeuchi K, Nagata Y, Sakakibara M, Ushida K, Ozone C, Enomoto A, Kawamoto I, Itagaki I, Tsuchiya H, Arima H, Wakabayashi T.
    A new primate model of hypophyseal dysfunction
    Sci Rep. 2021 May 24;11(1):10729.
  • Yoshioka N, Tanaka M, Ochi K, Watanabe A, Ono K, Sawada M, Ogi T, Itoh M, Ito A, Shiraki Y, Enomoto A, Ishigami M, Fujishiro M, Ogawa Y, Suganami T.
    The sodium-glucose cotransporter-2 inhibitor Tofogliflozin prevents the progression of nonalcoholic steatohepatitis-associated liver tumors in a novel murine model
    Biomed Pharmacother. 2021 Aug;140:111738. doi: 10.1016/j.biopha.2021.111738.
  • Yasuda Y, Iwama S, Sugiyama D, Okuji T, Kobayashi T, Ito M, Okada N, Enomoto A, Ito S, Yan Y, Sugiyama M, Onoue T, Tsunekawa T, Ito Y, Takagi H, Hagiwara D, Goto M, Suga H, Banno R, Takahashi M, Nishikawa H, Arima H.
    CD4+ T cells are essential for the development of destructive thyroiditis induced by anti-PD-1 antibody in thyroglobulin-immunized mice
    Sci Transl Med. 2021 May 12;13(593):eabb7495.
  • Hara A, Kato K, Ishihara T, Kobayashi H, Asai N, Mii S, Shiraki Y, Miyai Y, Ando R, Mizutani Y, Iida T, Takefuji M, Murohara T, Takahashi M, Enomoto A.
    Meflin defines mesenchymal stem cells and/or their early progenitors with multilineage differentiation capacity
    Genes Cells. 2021 May 7. doi: 10.1111/gtc.12855.
  • Kobayashi H, Gieniec KA, Wright JA, Wang T, Asai N, Mizutani Y, Iida T, Ando R, Suzuki N, Lannagan TRM, Ng JQ, Hara A, Shiraki Y, Mii S, Ichinose M, Vrbanac L, Lawrence MJ, Sammour T, Uehara K, Davies G, Lisowski L, Alexander IE, Hayakawa Y, Butler LM, Zannettino ACW, Din MO, Hasty J, Burt AD, Leedham SJ, Rustgi AK, Mukherjee S, Wang TC, Enomoto A, Takahashi M, Worthley DL, Woods SL.
    The Balance of Stromal BMP Signaling Mediated by GREM1 and ISLR Drives Colorectal Carcinogenesis
    Gastroenterology. 2021 Mar;160(4):1224-1239.e30
  • Ohara Y, Enomoto A, Tsuyuki Y, Sato K, Iida T, Kobayashi H, Mizutani Y, Miyai Y, Hara A, Mii S, Suzuki J, Yamashita K, Ito F, Motooka Y, Misawa N, Fukui T, Kawaguchi K, Yokoi K, Toyokuni S.
    Connective tissue growth factor produced by cancer‑associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma.
    Oncol Rep. 2020 Sep;44(3):838-848.
  • Chen C, Enomoto A, Weng L, Taki T, Shiraki Y, Mii S, Ichihara R, Kanda M, Koike M, Kodera Y, Takahashi M.
    Complex roles of the actin-binding protein Girdin/GIV in DNA damage-induced apoptosis of cancer cells.
    Cancer Sci. 2020 Nov;111(11):4303-4317.
  • Esaki N, Enomoto A, Takagishi M, Mizutani Y, Iida T, Ushida K, Shiraki Y, Mii S, Takahashi M.
    The Daple-CK1ε complex regulates Dvl2 phosphorylation and canonical Wnt signaling.
    Biochem Biophys Res Commun. 2020 Nov 12;532(3):406-413.
  • Taki T, Shiraki Y, Enomoto A, Weng L, Chen C, Asai N, Murakumo Y, Yokoi K, Takahashi M, Mii S.
    CD109 regulates in vivo tumor invasion in lung adenocarcinoma through TGF-β signaling.
    Cancer Sci. 2020 Dec;111(12):4616-4628.
  • Miyai Y, Esaki N, Takahashi M, Enomoto A.
    Cancer-associated fibroblasts that restrain cancer progression: Hypotheses and perspectives.
    Cancer Sci. 2020 Apr;111(4):1047-1057.
  • Hirabayashi S, Hayashi M, Nakayama G, Mii S, Hattori N, Tanabe H, Kanda M, Tanaka C, Kobayashi D, Yamada S, Koike M, Fujiwara M, Takahashi M, Kodera Y.
    The Significance of Molecular Biomarkers on Clinical Survival Outcome Differs Depending on Colon Cancer Sidedness.
    Anticancer Res. 2020 Jan;40(1):201-211.
  • Takagishi M, Esaki N, Takahashi K, Takahashi M.
    Cytoplasmic Dynein Functions in Planar Polarization of Basal Bodies within Ciliated Cells.
    iScience. 2020 Jun 26;23(6):101213.
  • Sakurai Y, Ichinoe M, Yoshida K, Nakazato Y, Saito S, Satoh M, Nakada N, Sanoyama I, Umezawa A, Numata Y, Shi-Xu J, Ichihara M, Takahashi M, Murakumo Y.
    Inactivation of REV7 enhances chemosensitivity and overcomes acquired chemoresistance in testicular germ cell tumors.
    Cancer Lett. 2020 Jun 15;489:100-110.
  • Mizutani Y, Kobayashi H, Iida T, Asai N, Masamune A, Hara A, Esaki N, Ushida K, Mii S, Shiraki Y, Ando K, Weng L, Ishihara S, Ponik SM, Conklin MW, Haga H, Nagasaka A, Miyata T, Matsuyama M, Kobayashi T, Fujii T, Yamada S, Yamaguchi J, Wang T, Woods SL, Worthley D, Shimamura T, Fujishiro M, Hirooka Y, Enomoto A, Takahashi M.
    Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis.
    Cancer Res. 2019 Oct 15;79(20):5367-5381.
  • Li J, Enomoto A, Weng L, Sun L, Takahashi M.
    Dephosphorylation of Girdin by PP2A inhibits breast cancer metastasis.
    Biochem Biophys Res Commun. 2019 May 21;513(1):28-34.
  • Ranjit M, Hirano M, Aoki K, Okuno Y, Ohka F, Yamamichi A, Kato A, Maeda S, Motomura K, Matsuo K, Enomoto A, Ino Y, Todo T, Takahashi M, Wakabayashi T, Kato T, Natsume A.
    Aberrant Active cis-Regulatory Elements Associated with Downregulation of RET Finger Protein Overcome Chemoresistance in Glioblastoma.
    Cell Rep. 2019 Feb 26;26(9):2274-2281.e5.
  • Kobayashi H, Enomoto A, Woods SL, Burt AD, Takahashi M,
    Worthley DL. Cancer-associated fibroblasts in gastrointestinal cancer. Nat Rev Gastroenterol Hepatol. 2019 May;16(5):282-295.
  • Ohno T, Miyasaka Y, Kuga M, Ushida K, Matsushima M, Kawabe T, Kikkawa Y, Mizuno M, Takahashi M.
    Mouse NC/Jic strain provides novel insights into host genetic factors for malaria research.
    Exp Anim. 2019 Aug 14;68(3):243-255.
  • Mii S, Enomoto A, Shiraki Y, Taki T, Murakumo Y, Takahashi M.
    CD109: a multifunctional GPI-anchored protein with key roles in tumor progression and physiological homeostasis.
    Pathol Int. 2019 May;69(5):249-259.
  • Hara A, Kobayashi H, Asai N, Saito S, Higuchi T, Kato K, Okumura T, Bando YK, Takefuji M, Mizutani Y, Miyai Y, Saito S, Maruyama S, Maeda K, Ouchi N, Nagasaka A, Miyata T, Mii S, Kioka N, Worthley DL, Murohara T, Takahashi M, Enomoto A.
    Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin in Cardiac Tissue Repair and the Development of Diastolic Dysfunction.
    Circ Res. 2019 Aug2;125(4):414-430.
  • Nakamura N, Naruse K, Kobayashi Y, Miyabe M, Saiki T, Enomoto A, Takahashi M, Matsubara T.
    Chemerin promotes angiogenesis in vivo.
    Physiol Rep. 2018 Dec;6(24):e13962.
  • Wang X, Enomoto A, Weng L, Mizutani Y, Abudureyimu S, Esaki N, Tsuyuki Y, Chen C, Mii S, Asai N, Haga H, Ishida S, Yokota K, Akiyama M, Takahashi M.
    Girdin/GIV regulates collective cancer cell migration by controlling cell adhesion and cytoskeletal organization.
    Cancer Sci. 2018 Nov;109(11):3643-3656.
  • Yasuda Y, Iwama S, Kiyota A, Izumida H, Nakashima K, Iwata N, Ito Y, Morishita Y, Goto M, Suga H, Banno R, Enomoto A, Takahashi M, Arima H, Sugimura Y.
    Critical role of rabphilin-3A in the pathophysiology of experimental lymphocytic neurohypophysitis.
    J Pathol. 2018 Apr;244(4):469-478.
  • Shindo A, Audrey A, Takagishi M, Takahashi M, Wallingford JB, Kinoshita M.
    Septin-dependent remodeling of cortical microtubule drives cell reshaping during epithelial wound healing.
    J Cell Sci. 2018 Jun 28;131(12):jcs212647.
  • Mii S, Hoshino A, Enomoto A, Murakumo Y, Ito M, Yamaguchi A, Takahashi M.
    CD109 deficiency induces osteopenia with an osteoporosis-like phenotype in vivo.
    Genes Cells. 2018 Jul;23(7):590-598.
  • Abudureyimu S, Asai N, Enomoto A, Weng L, Kobayashi H, Wang X, Chen C, Mii S, Takahashi M.
    Essential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure.
    Sci Rep. 2018 May 8;8(1):7292.
  • Weng L, Han YP, Enomoto A, Kitaura Y, Nagamori S, Kanai Y, Asai N, An J, Takagishi M, Asai M, Mii S, Masuko T, Shimomura Y, Takahashi M.
    Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex.
    PLoS Biol. 2018 Mar 14;16(3):e2005090.
  • Maegawa T, Miyasaka Y, Kobayashi M, Babaya N, Ikegami H, Horio F, Takahashi M, Ohno T.
    Congenic mapping and candidate gene analysis for streptozotocin-induced diabetes susceptibility locus on mouse chromosome 11.
    Mamm Genome. 2018 Apr;29(3-4):273-280.
  • Mizutani Y, Kuga D, Iida M, Ushida K, Takagi T, Tokita Y, Takahashi M, Asai M.
    Use of Anti-phospho-girdin Antibodies to Visualize Intestinal Tuft Cells in Free-Floating Mouse Jejunum Cryosections.
    J Vis Exp. 2018 Mar 21;(133):57475.
  • Esaki N, Ohkawa Y, Hashimoto N, Tsuda Y, Ohmi Y, Bhuiyan RH, Kotani N, Honke K, Enomoto A, Takahashi M, Furukawa K, Furukawa K.
    ASC amino acid transporter 2,defined by enzyme-mediated activation of radical sources, enhances malignancy of GD2-positive small-cell lung cancer.
    Cancer Sci. 2018 Jan;109(1):141-153.
  • Ushida K, Asai N, Uchiyama K, Enomoto A, Takahashi M.
    Development of a method to preliminarily embed tissue samples using low melting temperature fish gelatin before sectioning: A technical note.
    Pathol Int. 2018 Apr;68(4):241-245.
  • Shiraki Y, Mii S, Enomoto A, Momota H, Han YP, Kato T, Ushida K, Kato A, Asai N, Murakumo Y, Aoki K, Suzuki H, Ohka F, Wakabayashi T, Todo T, Ogawa S, Natsume A and Takahashi M.
    Significance of perivascular tumour cells defined by CD109 expression in progression of glioma.
    J. Pathol. 243: 468-480 (2017).
  • Takagishi, M., Sawada, M., Ohata, S., Asai, N., Enomoto, A., Takahashi, K., Weng, L., Ushida, K., Ara, H., Matsui, S., Kaibuchi, K., Sawamoto, K. and Takahashi, M.
    Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus.
    Cell Rep. 20: 960-972 (2017).
  • Kuga, D., Ushida, K., Mii, S., Enomoto, A., Asai, N., Nagino, M., Takahashi, M. and Asai, M.
    Tyrosine phosphorylation of an actin-binding protein Girdin specifically marks tuft cells in human and mouse gut.
    J. Histochem. Cytochem. 65: 347-366 (2017).
  • Han, Y-P., Enomoto, A., Shiraki, Y., Wang, S-Q., Wang, X., Toyokuni, S., Asai, N., Ushida, K., Hosne, A., Ohka, F., Wakabayashi, T., Ma, J., Natsume, A. and Takahashi, M.
    Significance of low mTORC1 activity in defining the characteristics of brain tumor stem cells.
    Neuro-Oncology 19: 636-647 (2017) .
  • Itoh, N., Enomoto, A., Nagai, T., Takahashi, M. and Yamada, K.
    Molecular mechanism linking BDNF/TrkB signaling with the NMDA receptor in memory: the role of Girdin in the CNS.
    Rev. Neurosci. 27: 481-490 (2016).
  • Wang, X., Enomoto, A., Asai, N., Kato, T. and Takahashi, M.
    Collective invasion of cancer: Perspectives from pathology and development.
    Pathol. Int. 66: 183-192 (2016).
  • Nakai, T., Kawasaki, T., Tada, T., Ishida, M., Iwakoshi, A., Enomoto, A., Okuda, S., Takahashi, M., Ambo, J.I., Sugai, T., Ohbayashi, C. and Ichihara, S.
    Well-differentiated neuroendocrine tumor of the breast with extensive lymphatic and vascular infiltration.
    Pathol. Int. 66: 706-707 (2016).
  • Sunagawa M, Mii S, Enomoto A, Kato T, Murakumo Y, Shiraki Y, Asai N, Asai M, Nagino M, and Takahashi M.
    Suppression of skin tumorigenesis in CD109-deficient mice.
    Oncotarget 7: 82836-82850 (2016).
  • Nogimori, K., Hori, T., Kawaguchi, K., Fukui, T., Mii, S., Nakada, H., Matsumoto, Y., Yamauchi, Y., Takahashi, M., Furukawa, K., Okajima, T., Yokoi, K., Hasegawa, Y. and Furukawa, K.
    Increased expression levels of ppGalNAc-T13 in lung cancers: Significance in the prognostic diagnosis.
    Int. J. Oncol. 49: 1369-1376 (2016) .
  • Maeda, K., Enomoto, A., Hara, A., Asai, N., Kobayashi, T., Horinouchi, A., Maruyama, S., Ishikawa, Y., Nishiyama, T., Kiyoi, H., Kato, T., Ando, K., Weng, L., Mii, S., Asai, M., Mizutani, Y., Watanabe, O., Hirooka, Y., Goto, H. and Takahashi, M.
    Identification of Meflin as a potential marker for mesenchymal stromal cells.
    Sci. Rep. 6: 22288 (2016).
  • Nahorski, M.S, Asai, M., Wakeling, E., Parker, A., Asai, N., Canham, N., Holder, S.E., Chen, Y.C., Dyer, J., Brady, A.F., Takahashi, M. and Woods, C.G.
    CCDC88A mutations cause PEHO-like syndrome in humans and mouse.
    Brain 139: 1036-1044 (2016).
  • Sakakura, H., Mii, S., Hagiwara, S., Kato, T., Yamamoto, N., Hibi, H., Takahashi, M. and Murakumo, Y.
    CD109 is a component of exosome secreted from cultured cells.
    Biochem. Biophys. Res. Commun. 469: 816-822 (2016).
  • Ara, H., Takagishi, M., Enomoto, A., Asai, M., Ushida, K., Asai, N., Shimoyama, Y., Kaibuchi, K., Kodera, Y. and Takahashi, M.
    Role for Daple in non-canonical Wnt signaling during gastric cancer invasion and metastasis.
    Cancer Sci. 107: 133-139 (2016).
  • Yamamura Y, Asai N, Enomoto A, Kato T, Mii S, Kondo Y, Ushida K., Niimi, K, Tsunoda N, Nagino M, Ichihara S, Furukawa K, Maeda K, Murohara T, Takahashi M.
    Akt-Girdin signaling in cancer-associated fibroblasts contributes to tumor progression.
    Cancer Res. 75: 813-823 (2015).
  • Takashima S, Kanatsu-Shinohara M, Tanaka T, Morimoto H, Inoue K, Ogonuki N, Jijiwa M, Takahashi M, Ogura A, Shinohara T.
    Functional Differences between GDNF-Dependent and FGF2-Dependent Mouse Spermatogonial Stem Cell Self-Renewal.
    Stem Cell Rep. 4: 489-502 (2015).
  • Mansour MA, Hyodo T, Ito S, Kurita K, Kokuryo T, Uehara K, Nagino M, Takahashi M, Hamaguchi M, Senga, T.
    SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling.
    FEBS J. 282: 1394-1405 (2015).
  • Omori K, Asai M, Kuga D, Ushida K, Izuchi T, Mii S, Enomoto A, Asai N, Nagino M, Takahashi M.
    Girdin is phosphorylated on tyrosine 1798 when associated with structures required for migration.
    Biochem. Biophys. Res. Commun. 458: 934-940 (2015).
  • Zhang J-M, Murakumo Y, Hagiwara S, Jiang P, Mii S, Kalyoncu E, Saito S, Suzuki C, Sakurai Y, Numata Y, Yamamoto T, Takahashi, M.
    CD109 attenuates TGFbeta1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells.
    Biochem. Biophys. Res. Commun. 459: 252-258 (2015).
  • Noda T, Maeda K, Hayano S, Asai N, Enomoto A, Takahashi M, Murohara, T.
    A new ER stress regulator, Gipie, regulates the survival of vascular smooth muscle cells and the neointima formation after vascular injury.
    Arterioscler. Thromb. Vasc. Biol. 35: 1246-1253 (2015).
  • Ichimiya H, Maeda K, Enomoto A, Weng L, Takahashi M, Murohara, T.
    Girdin/GIV regulates transendothelial permeability by controlling VE-cadherin trafficking through the small GTPase, R-Ras.
    Biochem. Biophys. Res. Commun. 461: 260-267 (2015).
  • Iwama S, Sugimura Y, Kiyota A, Kato T, Enomoto A, Suzuki H, Iwata N, Takeuchi S, Nakashima K, Takagi H, Izumida H, Ochiai H, Fujisawa H, Suga H, Arima H, Shimoyama Y, Takahashi M, Nishioka H. Ishikawa SE, Shimatsu A, Caturegli P, Oiso Y.
    Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis
    J. Clin. Endocrinol .Metab. 100: E946-54 (2015).
  • Muramatsu A, Enomoto A, Kato T, Weng L, Kuroda K, Asai N, Asai M, Mii S, Takahashi M.
    Potential involvement of kinesin-1 in the regulation of subcellular localization of Girdin.
    Biochem Biophys Res Commun. 463: 999-1005 (2015).
  • Hayano S, Takefuji M, Maeda K, Noda T, Ichimiya H, Kobayashi K, Enomoto A, Asai N, Takahashi M, Murohara, T.
    Akt-dependent Girdin phosphorylation regulates repair processes after acute myocardial infarction.
    J Mol Cell Cardiol. 88: 55-63 (2015)
  • Nakai T, Nagai T, Tanaka M, Itoh N, Asai N, Enomoto A, Asai M, Yamada S, Saifullah AB, Sokabe M, Takahashi M, Yamada, K.
    Girdin phosphorylation is crucial for synaptic plasticity and memory: Potential role in the interaction of BDNF/TrkB/Akt signaling with NMDA receptor.
    J Neurosci. 34: 14995-15008 (2014).
  • Weng L, Enomoto A, Miyoshi H, Takahashi K, Asai N, Morone N, Jiang P, An J, Kato T, Kuroda K, Watanabe T, Asai M, Ishida-Takagishi M, Murakumo Y, Nakashima H, Kaibuchi K, Takahashi M.
    Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein girdin.
    EMBO J. 33: 2098-2112 (2014).
  • Ota H, Hikita T, Sawada M, Nishioka T, Matsumoto M, Komura M, Ohno A, Kamiya Y, Miyamoto T, Asai N, Enomoto A, Takahashi M, Kaibuchi K, Sobue K, Sawamoto. K.
    Speed control for neuronal migration in the postnatal brain by Gmip-mediated local inactivation of RhoA.
    Nat Commun. July 30;5:4532 (2014).
  • Han YP, Ma CK, Wang SQ, Enomoto A, Zhao Y, Takahashi M, Ma J.
    Evaluation of osteopontin as a potential biomarker for central nervous system embryonal tumors.
    J Neuro-Oncol. 119:343-351 (2014).
  • Kato T, Enomoto A, Watanabe T, Haga H, Ishida S, Kondo Y, Furukawa K, Urano T, Mii S, Weng L, Ishida-Takagishi M, Asai M, Asai N, Kaibuchi K, Murakumo Y, Takahashi M.
    TRIM27/MTRF-B-dependent integrin beta1 expression defines leading cells in cancer cell collecitives.
    Cell Rep. 7:1156-1167 (2014)
  • Niimi K, Murakumo Y, Watanabe N, Kato T, Mii S, Enomoto A, Asai M, Asai N, Yamamoto E, Kajiyama H, Shibata K, Kikkawa F, Takahashi M.
    Suppression of REV7 enhances cisplatin sensitivity in ovarian clear cell carcinoma cells
    Cancer Sci. 105:545-552 (2014).
  • Hagiwara D, Arima H, Morishita Y, Wenjun L, Azuma Y, Ito Y, Suga H, Goto M, Banno R, Sugimura Y, Shiota A, Asai N, Takahashi M, Oiso Y.
    Arginine vasopressin neuronal loss results from autophagy-associated cell death in a mouse model for familial neurohypophysial diabetes insipidus.
    Cell Death and Disease 5:e114 (2014).
  • Miyachi H, Mii S, Enomoto A, Murakumo Y, Kato T, Asai N, Komori K, Takahashi M.
    Role of Girdin in intimal hyperplasia in vein grafts and efficacy of atelocollagen-mediated application of siRNA for vein failure.
    J Vasc Surg. 60:479-489.e5 (2014).
  • Nishimae K, Tsunoda N, Yokoyama Y, Kokuryo T, Iwakoshi A, Takahashi M, Nagiono, M.
    The impact of Girdin expression on recurrence-free survival in patients with luminal-type breast cancer.
    Breast Cancer in press
  • Qiao S, Fan K, Iwashita T, Ichihara M, Yoshino M, Takahashi M.
    The involvement of reactive oxygen species derived from NADPH oxidase-1 activation on the constitutive tyrosine auto-phosphorylation of RET proteins.
    Free Radic Res. 48:427-34 (2014).
  • Sakakura H, Murakumo Y, Mii S, Hagiwara S, Kato T, Asai M, Hoshino A, Yamamoto N, Sobue S, Ichihara M, Ueda M, Takahashi M.
    Detection of a soluble form of CD109 in serum of CD109 transgenic and tumor xenografted mice.
    PLoS One. 9:e83385 (2014).
  • Takahara Y, Maeda M, Hasegawa H, Ito S, Hyodo T, Asano E, Takahashi M, Hamaguchi M, Senga T.
    Silencing of TBC1D15 promotes RhoA activation and membrane blebbing.
    Mol Cell Biochem. 389:9-16 (2014).
  • Ueno S, Nishiguchi KM, Tanioka H, Enomoto A, Yamanouchi T, Kondo M, Yasuma TR, Yasuda S, Kuno N, Takahashi M, Terasaki H.
    Degeneration of retinal on bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy.
    PLoS One. 8:e81507 (2013).
  • Ota H, Hikita T, Nishioka T, Matsumoto M, Ito J, Asai N, Enomoto A, Takahashi M, Kaibuchi K, Sobue K, Sawamoto K.
    Proteomic analysis of Girdin-interacting proteins in migrating new neurons in the postnatal mouse brain.
    Biochem Biophys Res Commun. 442:16-21 (2013).
  • Hoshino A, Hanada S, Yamada H, Mii S, Takahashi M, Mitarai S, Yamamoto K, Manome Y.
    Mycobacterium tuberculosis escapes from the phagosomes of infected human osteoclasts reprograms osteoclast development via dysregulation of cytokines and chemokines.
    Pathog Dis. 70:28-39 (2014).
  • Asano E, Hasegawa H, Hyodo T, Ito S, Maeda M, Takahashi M, Hamaguchi M, Senga T.
    The Aurora-B-mediated phosphorylation of SHCBP1 regulates cytokinetic furrow ingression.
    J Cell Sci. 126:3263-3270 (2013).
  • Hagiwara S, Yamamoto N, Furue H, Sakakura H, Shigetomi T, Murakumo Y, Hibi H, Takahashi M, Ueda M.
    Pathological analysis of Ki-67 and CD109 expression in tongue squamous cell carcinoma.
    J Oral Maxillofac Surg Med Pathol. 25:276-281 (2013).
  • Watanabe, N., Mii, S., Asai, N., Asai, M., Niimi, K., Ushida, K., Kato, T., Enomoto, A., Ishii, H., Takahashi, M., and Murakumo, Y,
    The REV7 subunit of DNA polymerase ζ is essential for primordial germ cell maintenance in the mouse.
    J. Biol. Chem.288:10459-10471 (2013).
  • Ito, T., Komeima, K., Yasuma, T., Enomoto, A., Asai, N., Iwase, S., Takahashi, M. and Terasaki, H.
    Girdin and its phosphorylation dynamically regulate neonatal vascular development and pathological neovascularization in the retina.
    Am. J. Pathol. 182: 586-596 (2013).
  • An, J., Enomoto, A., Weng, L., Kato, T., Iwakoshi, A., Ushida, K., Maeda, K., Ishida-Takagishi, M., Ishii, G., Ming, S., Sun, T. and Takahashi, M.
    Significance of cancer-associated fibroblasts in the regulation of gene expression in the leading cells of invasive lung cancer.
    J. Cancer Res. Clin. Oncol. 139: 379-388 (2013).
  • Muteliefu G, Shimizu H, Enomoto A, Nishijima F, Takahashi M, Niwa T.
    Indoxyl sulfate promotes vascular smooth muscle cell senescence with upregulation of p53, p21, and prelamin A through oxidative stress.
    Am J Physiol Cell Physiol. 303:C126-134 (2012).
  • Mao, J.-Z., Jiang, P., Cui, S.-P., Ren, Y.-L., Zhao, J., Yin, X.-H., Enomoto, A., Liu, H.-J., Hou, L., Takahashi, M. and Zhang, B.
    Girdin locates in centrosome and midbody and plays an important role in cell division.
    Cancer Sci. 103: 1780-1787 (2012).
  • Horio-Sakurai, M., Kato, T., Mii, S., Enomoto, A., Asai, M., Asai, N., Murakumo, Y., Shibata, K., Kikkawa, F. and Takahashi, M.
    Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer.
    Cancer Med. 1: 218-229 (2012).
  • Asai M., Asai, N., Murata, A., Yokota, H., Ohmori, K., Mii, S., Enomoto, A., Murakumo, Y. and Takahashi, M.
    Similar Phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage.
    Biochem. Biophys. Res. Commun. 426: 533-538 (2012).
  • Hyodo T, Ito S, Hasegawa H, Asano E, Maeda M, Urano T, Takahashi M, Hamaguchi M, Senga T.
    Misshapen-like kinase 1 (MINK1) Is a Novel Component of Striatin-interacting Phosphatase and Kinase (STRIPAK) and Is Required for the Completion of Cytokinesis.
    J. Biol. Chem. 287: 25019-25029 (2012).
  • Mii, S., Murakumo, Y., Asai, N., Jijiwa, M., Hagiwara, S., Kato, T., Asai, M., Enomoto, A., Ushida, K., Sobue, S., Ichihara, M. and Takahashi, M.
    Epidermal hyperplasia and appendage abnormalities in mice lacking CD109.
    Am. J. Pathol. 181: 1180-1189 (2012).
  • Muteliefu, G., Shimizu, H., Enomoto, A., Nishijima, F., Takahashi, M. and Niwa, T.
    Indoxyl sulfate promotes vascular smooth muscle cell senescence with upregulation of p53, p21 and prelamin A through oxidative stress.
    Am. J. Physiol. Cell Physiol. 303: C126-C134 (2012).
  • Ishida-Takagishi, M., Enomoto, A., Asai, N., Ushida, K., Watanabe, T., Hashimoto, T., Kato, T., Weng, L., Matsumoto, S., Asai, M., Murakumo, y., Kaibuchi, K., Kikuchi, A. and Takahashi, M.
    The Dvl-associated protein Daple controls the non-canonical Wnt/Rac pathway and cell motility.
    Nature Commun. 3: 859 (2012).
  • Ohara, K., Enomoto, A., Kato, T., Hashimoto, T., Isotani-Sakakibara, M., Asai, N., Ishida,-Takagishi, M., Weng, L., Nakayama, M., Watanabe, T., Kato, K., Kaibuchi, K., Murakumo, Y., Hirooka, Y., Goto, H. and Takahashi M.
    Involvement of Girdin in the dermination of cell polarity during cell migration.
    PLoS One, 7: e36681 (2012).
  • Iwakoshi A., Murakumo Y., Kato T., Kitamura A., Mii S., Saito S., Yatabe Y., Takahashi M.
    RET finger protein expression is associated with prognosis in lung cancer with epidermal growth factor receptor mutations.
    Pathol. Int. 62: 324-330 (2012).
  • Natsume, A., Kato, T., Kinjo, S., Enomoto, A., Toda, H., Shimato, S., Ohka, F., Motomura, K., Kondo, Y., Miyata, T., Takahashi, M. and Wakabayashi, T.
    Girdin maintains the stemness of glioblastoma stem cells.
    Oncogene 31: 2715-2724 (2012).
  • Ohgami, N., Ida-Eto, M., Sakashita, N., Sone, M., Nakashima, T., Tabuchi, K., Hoshino, T., Shimada, A., Tsuzuki, T., Yamamoto, M., Sobue, G., Jijiwa, M., Asai, N., Hara, A., Takahashi, M. and Kato, M.
    Partial impairment of c-Ret at tyrosine 1062 accelerates age-related hearing loss in mice.
    Neurobiol. Aging 33: 626 e25-34 (2012).
  • Kee, H. J., Kim, J-R, Joung, H., Choe, N., Lee, S. E., Eom, G. H., Kim, J. C., Geyer, S. H., Jijiwa, M., Kato, T., Kawai, K., Weninger, W. J., Seo, S. B., Nam, K-I., Jeong, M. H., Takahashi, M. and Kook, H.
    Ret finger protein inhibits muscle differentiation by modulating serum response factor and enhancer of polycomb 1.
    Cell Death Differ. 19: 121-131 (2012).
  • Nakamura, N., Naruse, K., Kobayashi, Y., Matsuki, T., Hamada, Y., Nakashima, E., Kamiya, H., Hata, M., Nishikawa, T., Enomoto, A., Takahashi, M., Murohara, T., Matsubara, T., Oiso, Y., Nakamura, J.
    High glucose impairs the proliferation and increases the apoptosis of endothelial progenitor cells by suppression of Akt.
    J. Diabetes Invest. 2: 262-270 (2011).
  • Asano, E., Maeda, M., Hasegawa, H., Ito, S., Hyodo, T., Yuan, H., Takahashi, H., Hamaguchi, M. and Senga, T.
    Role of palladin phosphorylation by extracellular signal-regulated kinase in cell migration.
    PLOS One 6: e29338 (2011).
  • Morishita, Y., Arima, H., Hiroi, M., Hayashi, M., Hagiwara, D., Asai, N., Ozaki, N., Sugiura, Y., Nagasaki, H., Shiota, A., Takahashi, M. and Oiso, Y.
    Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum.
    Endocrinology 152: 4846-4855 (2011).
  • Kuroda, K., Yamada, S., Tanaka, M., Iizuka, M., Yano, H., Mori, D., Tsuboi, D., Nishioka, T., Namba, T., Iizuka, Y., Kubota, S., Nagai, T., Ibi, D., Wang, R., Enomoto, A., Isotani-Sakakibara, M., Asai, N., Kimura, K., Kiyonari, H., Abe, T., Mizoguchi, A., Sokabe, M., Takahashi, M., Yamada, K. and Kaibuchi, K.
    Behavioral alterations associated with targeted disruption of exons 2 and 3 of the DISC1 gene in the mouse.
    Hum. Mol. Genet. 20: 4666-4683 (2011).
  • Huang, Z., Ichihara, S., Oikawa, S., Chang, J., Zhang, L., Takahashi, M., Subramanian, K., Mohideen, S. S., Wang, Y. and Ichihara, G.
    Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-bromoprpane.
    Toxicol. Appl. Pharmacol. 257: 93-101 (2011).
  • Motegi Y., Katayama K., Sakurai F., Kato T., Yamaguchi T., Matsui H., Takahashi M., Kawabata K., Mizuguchi H.
    An effective gene-knockdown using multiple shRNA-expressing adenovirus vectors.
    J. Control Release 153: 149-153 (2011).
  • Wang, Y., Kaneko, N., Asai, N., Enomoto, A., Isotani-Sakakibara, M., Kato, T., Asai, M., Murakumo, Y., Ota, H., Hikita, T., Namba, T., Kuroda, K., Kaibuchi, K., Ming, G., Song, H., Sawamoto, K. and Takahashi, M.
    Girdin is an intrinsic regulator of neuroblast chain migration in the rostral migratory stream of the postnatal brain.
    J. Neurosci. 31: 8109-8122 (2011).
  • Miyake, H., Maeda, K., Asai, N., Shibata, R., Ichimiya, H., Isotani-Sakakibara, M., Yamamura, Y., Kato, K., Enomoto, A., Takahashi, M. and Murohara, T.
    The actin-binding protein Girdin and its Akt-mediated phosphorylation regulate neointima formation after vascular injury.
    Circ. Res. 108: 1170-1179 (2011).
  • Matsushita, E., Asai, N., Enomoto, A., Kawamoto, Y., Kato, T., Mii, S., Maeda, K., Shibata, R., Hattori, S., Hagikura, M., Takahashi, k., Sokabe, M., Murakumo, Y., Murohara, T. and Takahashi, M.
    Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cell.
    Mol. Biol. Cell. 22: 736-747 (2011).
  • Miyamoto, R., Jijiwa, M., Asai, M., Kawai, K., Ishida-Takagishi, M., Mii, S., Asai, N., Enomoto, A., Murakumo, Y., Yoshimura, A. and Takahashi, M.
    Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis but not intestinal aganglionosis in Ret Y1062F mutant mice
    Dev. Biol.349: 160-168 (2011).
  • Saito, S., Murakumo, Y., Tsuzuki, T., Dambara, A., Kato, T., Enomoto, A., Asai, N., Maruyama, S., Matsuo, S. and Takahashi, M.
    Analysis of GDNF-inducible zinc finger protein 1 expression in human diseased kidney.
    Human Pathol. 42: 848-858 (2011).
  • Yamaguchi M., Suyari O., Nagai R., Takahashi M.
    dGirdin a new player of Akt /PKB signaling in Drosophila melanogaster.
    Front. Biosci. 15: 1164-1171 (2010).
  • Hagikura, M., Murakumo, Y., Hasegawa, M., Jijiwa, M., Hagiwara, S., Mii, S., Hagikura, S., Matsukawa, Y., Yoshino, Y., Hattori, R., Wakai, K., Nakamura, S., Gotoh, M. and Takahashi, M.
    Correlation of pathological grade and tumor stage of urothelial carcinoma with CD109 expression.
    Pathol. Int. 60: 735-743 (2010).
  • Ohgami, N., Ida-Eto, M., Shimotake, T., Sakashita, N., Sone, M., Nakashima, T., Tabuchi, K., Hoshino, T., Shimada, A., Tsuzuki, T., Yamamoto, M., Sobue, G., Jijiwa, M., Asai, N., Hara, A., Takahashi, M. and Kato, M.
    c-Ret-mediated hearing loss in mice with Hirschsprung disease.
    Proc. Natl. Acad. Sci. USA. 107: 13051-13056 (2010).
  • Hagiwara, S., Murakumo, Y., Mii, S., Shigetomi, T., Yamamoto, N., Furue, H., Ueda, M. and Takahashi,M.
    Processing of CD109 by furin and its role in the regulation of TGF-beta signaling.
    Oncogene 29: 2181-2191.(2010)
  • Kurotsuchi, A., Murakumo, Y., Jijiwa, M., Kurokawa, K., Itoh, Y., Kodama, Y., Kato, T., Enomoto, A.,Asai, N., Terasaki, H. and Takahashi, M.
    Analysis of DOK-6 function in downstream signaling of RET in human neuroblastoma cells.
    Cancer Sci. 101: 1147-1155 (2010).
  • Weng, L., Enomoto, A., Ishida-Takagishi, M., Asai, N. and Takahashi, M.
    Girding for migratory cues: Role of the Akt substrate Girdin in cancer progression and angiogenesis.
    Cancer Sci. 101: 836-842 (2010).
  • Kato, M., Takeda, K., Hossain, K., Thang, N.D., Kaneko, Y., Kumasaka, M., Yamanoshita, O., Uemura, N.,Takahashi, M., Ohgami, N., and Kawamoto, Y.
    A redox-linked novel pathway for arsenic-mediated RET tyrosine kinase activation.
    J. Cell. Biochem. 110: 399-407 (2010).
  • Ohshima, Y., Yajima, I., Kumasaka, M.Y., Yanagishita, T., Watanabe, D., Takahashi, M., Inoue, Y., Ihn, H., Matsumoto, Y. and Kato, M.
    CD109 expression levels in malignant melanoma.
    J. Dermatol. Sci. 57: 140-142 (2010).
  • Kumasaka, M.Y., Yajima, I., Hossain, K., Iida, M., Tsuzuki, T., Ohno, T., Takahashi, M., Yanagisawa,M. and Kato, M.
    A novel mouse model for de novo Melanoma.
    Cancer Res. 70: 24-29 (2010).
  • Muteliefu, G., Enomoto, A., Jiang, P., Takahashi, M., Niwa, T.
    Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells.
    Nephrol. Dial. Transplant. 24: 2051-2058 (2009).
  • Lu, B., Cebrian, C., Chi, X., Kuure, S., Kuo, R., Bates, C.M., Arber, S., Hassell, J., MacNeil, L., Hoshi, M., Jain, S., Asai, N., Takahashi, M., Schmidt-Ott, K., Barasch, J., D'Agati, V. and Costantini, F.
    Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis.
    Nature Genet. 41:1295-1302 (2009).
  • Puseenam, A., Yoshioka, Y., Nagai, R, Hashimoto, R, Suyari, O, Itoh, M, Enomoto, A, Takahashi, M. and Yamaguchi, M.
    A novel Drosophila Girdin-like protein is involved in Akt pathway control of cell size.
    Exp. Cell Res. 315:3370-3380 (2009).
  • Enomoto, A., Asai, N., Namba, T., Wang, Y., Kato, T., Tanaka, M., Tatsumi, H., Taya, S., Tsuboi, D., Kuroda, K., Kaneko, N., Sawamoto, K., Miyamoto, R., Jijiwa, M., Murakumo, Y., Sokabe, M., Seki, T., Kaibuchi, K. and Takahashi, M.
    Roles of Disrupted-in-Schizophrenia 1-interacting protein Girdin in postnatal development of the dentate gyrus.
    Neuron 63: 774-787 (2009).
  • Tsukamoto, H., Kato, T., Enomoto, A., Nakamura, N., Shimono, Y., Jijiwa, M., Asai, N., Murakumo, Y., Shibata, K., Kikkawa, F. and Takahashi, M.
    Expression of Ret finger protein correlates with outcomes in endometrial cancer.
    Cancer Sci. 100: 1895-1901 (2009).
  • Chi, X., Michos, O., Shakya, R., Riccio, P., Enomoto, H., Licht, J.D., Asai, N., Takahashi, M., Ohgami, N., Kato, M., Mendelsohn, C. and Costantini, F
    Ret-dependent cell rearrangements in the Wolffian duct epithelium initiate ureteric bud morphogenesis.
    Dev. Cell 17: 199-209 (2009).
  • Nakamura, N., Naruse, K., Matsuki, T., Hamada, Y., Nakashima, E., Kamiya, H., Matsubara, T., Enomoto, A., Takahashi, M, Oiso, Y. and Nakamura, J.
    Adiponectin promotes migration activities of endothelial progenitor cells via Cdc42/Rac1
    FEBS Lett. 583: 2457-2463 (2009).
  • Kato, T., Shimono, Y., Hasegawa, M., Jijiwa, M., Enomoto, A., Asai, N., Murakumo, Y. and Takahashi, M.
    Characterization of the HDAC1 complex that regulates the sensitivity of cancer cells to oxidative stress.
    Cancer Res. 69: 3597-3604 (2009).
  • Jiang, P., Enomoto, A. and Takahashi, M.
    Cell biology of the movement of breast cancer cells: intracellular signaling and the actin cytoskeleton.
    Cancer Lett. 284:122-130 (2009).
  • Hasegawa, T., Enomoto, A., Kato, T., Kawai, K., Miyamoto, R., Jijiwa, M., Ichiahara, M., Ishida, M., Asai, N., Murakumo, Y., Ohara, K., Niwa, Y., Goto, H., and Takahashi, M.
    Roles of induced expression of MAPK phosphatase-2 in tumor development in RET-MEN2A transgenic mice.
    Oncogene 27: 5684-5695 (2008).
  • Hagiwara, S., Murakumo, Y., Sato, T., Mitsudo, K., Tohnai, I., Ueda, M. and Takahashi, M.
    Up-regulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity.
    Cancer Sci. 99: 1916-1923 (2008).
  • Hasegawa, M., Moritani, S., Murakumo, Y., Sato, T., Hagiwara, S., Suzuki, C., Mii, S., Jijiwa, M., Enomoto, a., Asai, N., Ichihara, S. and Takahashi, M.
    CD109 expression in basal-like breast carcinoma.
    Pathol. Int. 58: 288-294 (2008).
  • Kitamura, T., Asai, N., Enomoto, A., Maeda, K., Kato, T., Ishida, M., Jiang, P., Watanabe, T., Usukura, J., Kondo, T., Costantini, F., Murohara, T. and Takahashi, M.
    Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin.
    Nature Cell Biol., 10:329-337(2008).
  • Jiang, P., Enomoto, A., Jijiwa, M., Kato, T., Hasegawa, T., Ishida, M., Sato, T., Asai, N., Murakumo, Y. and Takahashi, M.
    An actin-binding protein Girdin regulates the motility of breast cancer cells.
    Cancer Res., 68:1310-1318(2008).
  • Jijiwa, M., Kawai, K., Fukihara, J., Nakamura, A., Hasegawa, M., Suzuki, C., Sato, T., Enomoto, A., Asai, N., Murakumo, Y. and Takahashi, M.
    GDNF-mediated Signaling via RET Tyrosine 1062 is Essential for Maintenance of Spermatogonial Stem Cells.
    Genes Cells, 13:365-374(2008).
  • Suzuki, C., Murakumo, Y., Kawase, Y., Sato, T., Morinaga, T., Fukuda, N., Enomoto, A., Ichihara, M. and Takahashi, M.
    A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1.
    Biochem. Biophys. Res. Commun. 366: 226-232 (2008).
  • Ichihara, M., Murakumo, Y., Masuda, A., Matsuura, T., Asai, N., Jijiwa, M., Ishida, M., Shinmi, J., Yatsuya, H., Qiao, S., Takahashi, M. and Ohno, K.
    Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities.
    Nucleic Acids Res. 35: e123 (2007).
  • Sato, T. Murakumo, Y., Hagiwara, S., Jijiwa, M., Suzuki, C. and Takahashi, M.
    High level expression of CD109 in lung squamous cell carcinoma.
    Pathol. Int. 57: 719-724 (2007).
  • Dambara, A., Morinaga, T., Fukuda, N., Yamakawa, Y., Kato, T., Enomoto, A., Asai, N., Murakumo, Y., Matsuo, S. and Takahashi, M.
    Nucleolin modulates the subcellular localization of GDNF-inducible zinc finger protein 1 and its roles in transcription and cell proliferation.
    Exp. Cell Res. 313: 3755-3766 (2007).
  • Murakami, M., Ichihara, M., Sobue, S., Kikuchi, R., Ito H., Kimura, A., Iwasaki, T., Takagi, A., Kojima, T., Takahashi, M., Suzuki, M., Banno, Y., Nozawa, Y. and Murate, T.
    RET signaling-induced SPHK1 gene expression plays a role in both GDNF-induced differentiation and MEN2-type oncogenesis.
    J. Neurochem. 102: 1585-1594 (2007).
  • Li, B., Zhou, J., Hu, J., Jin, H., Shimono, Y., Takahashi, M. and Xu, G.
    Polycomb protein Cbx4 promotes SUMO modification of de novo DNA methyltransferase Dnmt3a.
    Biochem. J. 405: 369-378 (2007).
  • Ishida, M., Ichihara, M., Mii, S., Jijiwa, M., Asai, N., Enomoto, A., Kato, T., Majima, A., Jiang, P., Murakumo, Y. and Takahashi, M.
    Sprouty2 regulates growth and differentiation of human neuroblastoma cells through RET tyrosine kinase.
    Cancer Sci. 98: 815-821 (2007).
  • Hasegawa, M., Hagiwara, S., Sato, T., Jijiwa, M., Murakumo, Y., Maeda, M., Moritani, S., Ichihara, S. and Takahashi, M.
    CD109, a new marker for myoepithelial cells of mammary, salivary, and lacrimal glands and prostate basal cells
    Pathol. Int. 57: 245-250 (2007).
  • Kee, H. J., Kim, J-R., Nam, K-I., Park, H. Y., Shin, S., Kim, J. C., Shimono, Y., Takahashi, M., Jeong, M. H., Kim, N., Kim, K. K. and Kook, H.
    Enhancer of Polycomb1, a novel homeodomain only protein binding partner, induces skeletal muscle differentiation.
    J. Biol. Chem. 282: 7700-7709 (2007).
  • Kato, M., Ohgami, N., Kawamoto, Y., Tsuzuki, T., Hossain, K., Yanagishita, T., Ohshima, Y., Tsuboi, H., Yamanoshita, O., Matsumoto, Y., Takahashi, M. and Nakashima, I.
    Protective effect of hyperpigmented skin on UV-mediated cutaneous cancer development.
    J. Invest. Dermatol. 127: 1244-1249 (2007).
  • Asai, N., Fukuda, T., Wu, Z., Enomoto, A., Pachnis, V., Takahashi, M. and Costantini, F.
    Targeted mutation of serine 697 in the Ret tyrosine kinase causes migration defect of enteric neural crest cells.
    Development 133: 4507-4516 (2006).
  • Murakumo, Y., Jijiwa, M., Asai, N., Ichihara, M., and Takahashi, M.
    RET and neuroendocrine tumors.
    Pituitary 9: 179-192 (2006).
  • Enomoto, A., Jiang, P., and Takahashi, M.
    Girdin, a novel actin-binding protein, and its family of proteins posses versatile function in the Akt and Wnt signaling pathways.
    Ann. NY Acad. Sci., 1086: 169-184 (2006).
  • Kato, M., Takeda, K., Kawamoto, Y., Tsuzuki, T., Kato, Y., Ohno, T., Hossain, K., Iftakhar-E-Khuda, I., Ohgami, N., Isobe, K., Takahashi, M. and Nakashima, I.
    Novel hairless RET-transgenic mouse line with melanocytic nevi and anagen hair follicles.
    J. Invest. Dermatol. 126: 2547-2550 (2006).
  • Uchida, M., Enomoto, A., Fukuda, T., Kurokawa, K., Maeda, K., Kodama, Y., Asai, N., Hasegawa, T., Shimono, Y., Jijiwa, M., Ichihara, M., Murakumo, Y. and Takahashi, M.
    Dok-4 regulates GDNF-dependent neurite outgrowth through downstream activation of Rap1 and mitogen-activated protein kinase.
    J. Cell Sci. 119: 3067-3077 (2006).
  • Takeda, K., Kawamoto, Y., Okuno, Y, Kato, M., Takahashi, M., Suzuki, H., Isobe, K. and Nakashima, I.
    A PKC-mediated backup mechanism of the MXXCW motif-linked switch for initiating tyrosine kinase activities.
    FEBS Lett. 839-843 (2006).
  • Asai, N., Jijiwa, M., Enomoto, A., Kawai, K., Maeda, K., Ichihara, M. and Takahashi M.
    RET receptor signaling; Dysfunction in thyroid cancer and Hirschsprung’s disease.
    Pathol. Int. 56: 164-172 (2006).
  • Murakumo, Y., Mizutani, S., Yamaguchi, M., Ichihara, M. and Takahashi, M.
    Analyses of ultraviolet-induced focus formation of hREV1 protein. C Genes Cells 11: 193-205 (2006).
  • Zhang JM, Hashimoto M, Kawai K, Murakumo Y, Sato T, Ichihara M, Nakamura S, Takahashi M.
    CD109 expression in squamous cell carcinoma of the uterine cervix
    Pathol Int. 55: 165-169 (2005).
  • Shimono, K., Shimono, Y., Shimokata, K., Ishiguro, N., and Takahashi, M.
    Microspherule protein 1, Mi-2β, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription.
    J. Biol. Chem. 280: 39436-39447 (2005).
  • Enomoto, A., Murakami, H., Asai, N., Morone, N., Watanabe, T., Kawai, K., Murakumo, Y., Usukura, J., Kaibuchi, K., and Takahashi, M.
    Akt/PKB regulates actin organization and cell motility via Girdin/APE.
    Developmental Cell 9: 389-402 (2005).
  • Morinaga, T., Enomoto, A., Shimono, Y., Hirose, F., Fukuda, N., Dambara, A., Jijiwa, M., Kawai, K., Hashimoto, K., Ichihara, M., Asai, N., Murakumo, Y., Matsuo, S., and Takahashi, M.
    GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region.
    Nucleic Acids Res. 33: 4191-4201, 2005.
  • Matsuura, T., Shimono, Y., Kawai, K., Murakami, H., Urano, T., Niwa, Y., Goto, H., and Takahashi, M.
    PIAS proteins are involved in the SUMO-1 modification, intracellular translocation and transcriptional repressive activity of RET finger protein.
    Exp. Cell Res. 308: 65-77, 2005.
  • Fukuda, T., Asai, N., Enomoto, A., and Takahashi, M.
    Activation of c-Jun amino-terminal kinase by GDNF induces G2/M cell cycle delay linked with actin reorganization.
    Genes Cells, 10: 655-663, 2005.
  • Kodama, Y., Asai, N., Kawai, K., Jijiwa, M., Murakumo, Y., Ichihara, M., and Takahashi, T.
    The RET proto-oncogene: a molecular therapeutic target in thyroid cancer.
    Cancer Sci. 96:143-148, 2005.
  • Jijiwa, M., Fukuda, T., Kawai, K., Nakamura, A., Kurokawa, K., Murakumo, Y., Ichihara, M. and Takahashi, M.
    A targeting mutation of tyrosine 1062 in Ret causes a marked decrease of enteric neurons and renal hypoplasia.
    Mol. Cell. Biol. 24: 8026-8036 (2004).
  • Maeda, K., Murakami, H., Yoshida, R., Ichihara, M., Abe, A., Hirai, M., Murohara, T. and Takahashi, M.
    Biochemical and biological responses induced by coupling of Gab1 to phosphatidylinositol 3-kinase in RET-expressing cells.
    Biochem. Biophys. Res. Commun. 323: 345-354 (2004).
  • Kodama, Y., Murakumo, Y., Ichihara, M., Kawai, K., Shimono, Y. and Takahashi, M.
    Induction of CRMP-2 by GDNF and analysis of the CRMP-2 promoter region.
    Biochem. Biophys. Res. Commun. 320:108-115 (2004).
  • Hashimoto, T., Ichihara, M., Watanabe, T., Kawai, K., Koshikawa, K., Yuasa, N., Takahashi, T., Yatabe, Y., Murakumo, Y., Zhang, J.-m., Nimura, Y. and Takahashi, M.
    Expression of CD109 in human cancer.
    Oncogene 23: 3716-3720 (2004).
  • Kawamoto, Y., Takeda, K., Okuno, Y., Yamakawa, Y., Ito, Y., Taguchi, R., Kato, M., Suzuki, H., Takahashi, M. and Nakashima, I.
    Identification of RET autophosphorylation sites by mass spectrometry.
    J. Biol. Chem. 279: 14213-14224 (2004).
  • Kato, M., Takdea, K., Kawamoto, Y., Tsuzuki, T., Hossain, K., Tamakoshi, A., Kunisada, T., Kobayashi, Y., Ogino, K., Suzuki, H., Takahashi, M. and Nakahsima, I.
    c-Kit-targeting immunotherapy for hereditary melanoma in a mouse model.
    Cancer Res. 64: 801-806 (2004).
  • Ichihara, M., Murakumo, Y., and Takahashi, M.
    RET and neuroendocrine tumors.
    Cancer Lett. 204:197-211 (2004).
  • Shimono, Y., Murakami, H., Kawai, K., Wade, P.A., Shimokata, K. and Takahashi, M.
    Mi-2 associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities.
    J. Biol. Chem. 278: 51638-51645 (2003).
  • Kawai, K., Jijiwa, M., Shimono, Y., Kurokawa, K., Murakumo, Y., Ichihara, M. and Takahashi, M.
    Establishment and characterization of mouse mammary carcinoma cell lines expressing RET with a multiple endocrine neoplasia 2A mutation.
    Cancer Science 94: 992-997 (2003).
  • Fukuda, N., Ichihara, M., Morinaga, T., Kawai, K., Hayashi, H., Murakumo, Y., Matsuo, S. and Takahashi, M.
    Identification of a novel GDNF-inducible gene required for renal branching morphogenesis.
    J. Biol. Chem. 278: 50386-50392 (2003).
  • Shimoyama, Y., Morikawa, Y., Ichihara, M., Kodama, Y., Fukuda, N., Hayashi, H., Morinaga, T., Iwashita, T., Murakumoa, Y. and Takahashi, M.
    Identification of human SEP1 as a glial cell line-derived neurotrophic factor-inducible protein and its expression in the nervous system.
    Neuroscience 12: 899-906 (2003).
  • Kurokawa, K., Kawai, K., Hashimoto, M., Ito, Y. and Takahashi M.
    Cell signaling and gene expression mediated by RET tyrosine kinase.
    J. Int. Med. 253: 627-633(2003).
  • Ohshima, N., Takahashi, M. and Hirose, F.
    Identification of a human homologue of the DREF transcription factor with a potential role in regulation of the histone H1 gene.
    J. Biol. Chem. 278: 22928-22938(2003).
  • Kawajiri, A., Yasui, Y., Goto, H., Tatsuka, M., Takahashi, M., Nagata, K. and Inagaki, M.
    Functional significance of Aurora-B in the separation of type III intermediated filaments during cytokinsis.
    Mol. Biol. Cell. 14: 1489-1500(2003).
  • Nishikawa, M., Murakumo, Y., Imai, T., Kawai, K., Nagaya, M., Funahashi, H., Nakao, M. and Takahashi, M.
    Cys611Ser mutation in RET proto-oncogene is a kindred with medullary thyroid carcinoma and Hirschsprung’s disease.
    Eur. J. Human Genet. 11: 364-368(2003).
  • Nakayama, A., Murakami, H., Maeyama, N., Yamashiro, N., Sakakibara, A., Mori, N. and Takahashi, M.
    Role for RFX transcription factors in non-neuronal cell-specific inactivation of the microtubule-associated protein MAP1A promoter.
    J. Biol. Chem. 278: 233-240 (2003).
  • Iwahashi N1, Murakami H, Nimura Y, Takahashi M.
    Activation of RET tyrosine kinase regulates interleukin-8 production by multiple signaling pathways. Biochem Biophys Res Commun. 294(3):642-9.(2002).
  • Murakami, H., Yamamura, Y., Shimono, Y., Kawai, K., Kurokawa, K. and Takahashi, M.
    Role of Dok1 in cell signaling mediated by RET tyrosine kinase.
    J. Biol. Chem. 277: 32781-32790 (2002).
  • Watanabe, T., Ichihara, M., Hashimoto, M., Shimono, K., Shimoyama, Y., Nagasaka, T., Murakumo, Y., Murakami, H., Sugiura, H., Iwata, H., Ishiguro, N. and Takahashi, M.
    Characterization of gene expression induced by RET with MEN2A or MEN2B mutation.
    Am. J. Pathol. 161: 249-256 (2002).
  • Fukuda, T., Kiuchi, K. and Takahashi, M.
    Essential role for protein kinase A in Rac activity mediated by RET tyrosine kinase.
    J. Biol. Chem. 277: 19114-19121 (2002).
  • Kato, M., Takeda, K., Kawamoto, Y., Iwashita, T., Akhand, A.A., Senga, T., Yamamoto, M., Sobue, G., Hamaguchi, M., Takahashi, M. and Nakashima, I.
    Repair by Src kinase of functional-impaired RET with multiple endocrine neoplasia type 2A mutation with substitutions of tyrosines in the COOH-terminal kinase domain for phenylalanine.
    Cancer Res. 62: 2414-2422 (2002).
  • Iwahashi, N., Nagasaka, T., Tezel, G., Iwashita, T., Asai, N., Murakumo, Y., Kiuchi, K., Sakata, K., Nimura, Y. and Takahashi, M.
    Expression of glial cell line-derived neurotrophic factor correlates with perineural invasion of bile duct carcinoma.
    Cancer 94: 167-174 (2002).
  • Murakumo, Y., Ogura, Y., Ishii, H., Numata, S., Ichiahra, M., Croce, C. M., Fichel, R. and Takahashi, M.
    Interaction in the error-prone psot-replication repair proteins, hREV1, hREV3, and hREV7.
    J. Biol. Chem. 276: 35644-35661 (2001).
  • Kato, M., Takeda, K., Kawamoto, Y., Tsuzuki, T., Dai, Y., Nakayama, S., Toriyama, K., Tamada, Y., Takahashi, M. and Nakashima, I.
    RET tyrosine kinase enhances hair growth in association with promotion of melanogensis.
    Oncogene 20: 7536-7541 (2001).
  • Takahashi, M.
    The GDNF/RET signaling pathway and human diseases.
    Cysokine & Growth Factor Reviews 12: 361-373 (2001).
  • Iwashita, T., Kurokawa, K., Qiao, S., Murakami, H., Asai, N., Kawai, K., Hashimoto, M., Watanabe, T., Ichihara., M. and Takahashi, M.
    Functional analysis of RET with Hirschsprung's mutations affecting its kinase domain.
    Gastroenterology 121: 24-33 (2001).
  • Shigemitsu, K., Sekido, Y., Usami, N., Mori, S., Sato, M., Horio, Y., Hasegawa, Y., Bader, S.A., Gazdar, A.F., Minna, J.D., Hida, T., Yoshioka, H., Imaizumi, M., Ueda, Y., Takahashi, M. and Shimokata, K.
    Genetic alteration of the b-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion.
    Oncogene 20: 4249-4257 (2001).
  • Kurokawa, K., Iwashita, T., Murakami, H., Hayashi, H., Kawai, K. and Takahashi, M.
    Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction.
    Oncogene 20: 1929-1938 (2001).
  • Qiao, S., Iwashita, T., Furukawa, T., Yamamoto, M., Sobue, G. and Takahashi, M.
    Differential effects of leukocyte common antigen-related protein on biochmical and biological activities of RET-MEN2A and RET-MEN2B mutant proteins.
    J. Biol Chem. 276: 9460-9467 (2001).
  • Hayashi, Y., Iwashita, T., Murakami, H., Kato, Y., Kawai, K., Tohnai, I., Ueda, M. and Takahashi, M.
    Activation of BMK1 via tyrosine 1062 in RET by GDNF and MEN2A mutation.
    Biochem. Biophys. Res. Commun. 281: 682-689 (2001).
  • Shimono, Y., Murakami, H., Hasegawa, Y. and Takahashi, M.
    RFP is a transcriptional repressor and interacts with enhancer of polycomb that has dual transcriptional functions.
    J. Biol Chem. 275: 39411-39419. (2000).
  • Kawai, K., Iwashita, T., Murakami, H., Hiraiwa, N., Yoshiki, A., Kusakabe, M., Ono, K., Iida, K., Nakayama, A. and Takahashi, M.
    Tissue-specific carcinogenesis in transgenic mice expressing the RET proto-oncogene with a multiple endocrine neoplasia type 2A mutation.
    Cancer Res. 60: 5254-5260 (2000).
  • Hayashi, H., Ichihara, M., Iwashita, T., Murakami H., Shimono, Y., Kawai, K., Kurokawa K., Murakumo, Y., Imai, T., Funahashi, H., Nakao, A. and Takahashi, M.
    Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell-lined derived neurotrophic factor.
    Oncogene 19: 4469-4475 (2000).
  • Iwashita, T., Murakami, H., Kurokawa, K., Kawai, K., Miyauchi, A., Futami, H., Qiao, S., Ichihara, M. and Takahashi, M.
    A two-hit model for development of multiple endocrine neoplasia type 2B by RET mutations.
    Biochem. Biophys. Res. Commun. 268: 804-808 (2000).
  • Kato, M., Iwashita, T., Takeda, K., Akhand, A. A., Liu, W., Yoshihara, M., Asai N., Suzuki, H., Takahashi, M. and Nakashima, I.
    Ultraviolet light induces redox reaction-mediated dimerization and superactivation of oncogenic ret tyrosine kinases.
    Mol. Biol. Cell 11: 93-101 (2000).
  • Tezel, G. Nagasaka, T., Iwahashi, N., Asai N., Iwashita, T., Sakata, K. and Takahashi, M.
    Different nuclear/cytoplasmic distributions of RET finger protein (RFP) in different cell types.
    Pathol. Int. 49: 881-886 (1999)
  • Ishiguro, Y., Iwashita, T., Murakami, H., Asai, N., Iida, K., Goto, H., Hayakawa, T. and Takahashi, M.
    The role of amino acids surrounding tyrosine 1062 in Ret in specific binding of the Shc phosphtyrosine binding domain.
    Endocrinology 140: 3992-3998 (1999).
  • Murakami, H., Iwashita, T., Asai, N., Shimono, Y., Iwata, Y., Kawai, K. and Takahashi, M.
    Enhanced phosphatidylinositol 3-kinase activity and high phosphrylation state of its downstream signaling molecules mediated by Ret with the MEN 2B mutation.
    Biochem. Biophys. Res. Commun. 262: 68-75 (1999).
  • Iwata, Y., Nakayama, A., Murakami, H., Iwashita, T., Asai, N. and Takahashi, M.
    Characterization of the promoter region of the human RFP gene.
    Biochem. Biophys. Res. Commun. 261: 381-384 (1999).
  • Iwashita, T., Kato, M., Murakami, H., Asai, N., Ishiguro, Y., Ito, S., Iwata, Y., Kawai, K., Asai, M., Kurokawa, K., Kajita, H. and Takahashi, M.
    Biological and biochemical properties of Ret with kinase domain mutations identified in multiple endocrine neoplasia type 2B and familial medullary thyroid carcinoma.
    Oncogene 18: 3919-3922 (1999).
  • Nakayama, S., Iida, K., Tsuzuki, T., Iwashita, T., Murakami, H., Asai, N., Iwata, Y., Ichihara, M., Ito, S., Kawai, K., Asai, M., Kurokawa, K. and Takahashi M.
    Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow hematopoietic cells.
    Brit. J. Hematol. 105: 50-57 (1999).
  • Takahashi, M., Iwashita, T., Santoro, M., Lyonnet, S., Lenor, G. M. and Billaud, M.
    Co-segregation of MEN2 and Hirschsprung's disease: the same mutation of RET with both gain and loss-of-function?
    Hum. Mutat. 13: 331-336 (1999).
  • Murakami, H., Iwashita, T., Asai, N., Iwata, Y., Narumiya, S. and Takahashi, M.
    Rho-dependent and -independent tyrosine phosphorylation of focal adhesion kinase, paxillin and p130Cas mediated by Ret kinase.
    Oncogene 18: 1975-1982 (1999).
  • Ohyabu, A., Higo, K., Ye, C., Amo, H., Saito, M., Yagyu, S., Morita, H., Maeda, K., Serikawa, T., Takahashi, M. and Matsuyama, M.
    Genetic mapping of the thymoma susceptible locus, Tsr1, in BUF/Mna rats.
    J. Natl. Cancer Inst. 91: 279-282 (1999).
  • Kato, M., Liu, W., Asai, N., Hayakawa, A., Kozaki, K., Takahashi, M. and Nakashima, I.
    The herbal medicine Sho-saiko-to inhibits grrowth and metastasis of malignant melanoma primarily developed in ret-transgenic mice.
    J. Invest. Dermatol. 111: 640-644 (1998).
  • Kato, M., Takahashi, M., Asai, N., Liu, W., Shimizu, S., Iwamoto, T., Suzuki, H. and Nakashima, I.
    Transgenic mouse model for skin malignant melanoma.
    Oncogene 17: 1885-1888 (1998).
  • Takahashi, M., Asai, N., Iwashita, T., Murakami, H. and Ito, S.
    Mechanisms of development of multiple endocrine neoplasia type 2 and Hirschsprung’s disease.
    Recent Results in Cancer Research 154: 229-236 (1998).
  • Takahashi, M., Asai, N., Iwashita, T., Murakami, H. and Ito, S.
    Molecular mechanisms of development of multiple endocirine neoplasia 2 by RET mutations.
    J. Int. Med. 243: 509-513 (1998).
  • Nozaki, C., Asai, N., Murakami, H., Iwashita, T., Iwata, Y., Horibe, K., Klein, R.D., Rosenthal, A. and Takahashi, M.
    Calcium-dependent Ret activation by GDNF and neurturin.
    Oncogene 16, 293-299 (1998).
  • Ito, S., Iwashita, T., Asai, N., Murakami, H., Iwata, Y., Sobue, G. and Takahashi, M.
    Biological properties of Ret with cysteine mutations correlate with multiple endocrine neoplasia type 2A, familial medullary thyroid carcinoma, and Hirschsprung's disease phenotype.
    Cancer Res. 57, 2870-2872 (1997).
  • Klein, R.D., Sherman, D., Ho, W.-H., Stone, D., Bennett, G.L., Moffat, B., Vandlen, R., Simmons, L., Gu, Q., Hongo, A.-J., Devaux, B., Poulsen, K., Armanini, M., Nozaki, C., Asai, N., Goddard, A., Phillips, H., Henderson, C.E., Takahashi, M. and Rosenthal, A.
    A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor.
    Nature 387, 717-721 (1997).
  • Ohiwa, M., Murakami, H., Iwashita, T., Asai, N., Iwata, Y., Imai, T., Funahashi, H., Takagi, H. and Takahashi, M.
    Characterization of Ret-Shc-Grb2 complex induced by GDNF, MEN 2A and MEN 2B mutations.
    Biochem. Biophys. Res. Commun. 237, 747-751 (1997).
  • Iwashita, T., Murakami, H., Asai, N. and Takahashi, M.
    Mechanism of Ret dysfunction by Hirschsprung mutations affecting its extracellular domain.
    Hum. Mol. Genet. 5, 1577-1580 (1996).
  • Asai, N., Murakami, H., Iwashita, T. and Takahashi, M.
    A mutation at tyrosine 1062 in MEN2A-Ret and MEN2B-Ret impairs their transforming activity and association with Shc adaptor proteins.
    J. Biol. Chem. 271, 17644-17649 (1996).
  • Treanor, J.J.S., Goodman, L., de Sauvage, F., Stone, D.M., Poulsen, K.T., Beck, C.D., Gray, C., Armanini, M.P., Pollock, R.A., Hefti, F., Phillips, H.S., Goddard, A., Moore, M.W., Buj-Bello, A., Davies, A.M. Asai, N., Takahashi, M., Vandlen, R., Henderson, C.E. and Rosenthal, A.
    Characterization of a multicomponent receptor for GDNF.
    Nature 382, 80-83 (1996).
  • Iwashita, T., Asai, N., Murakami, H., Matsuyama, M. and Takahashi, M.
    Identification of tyrosine residues that are essential for transforming activity of the ret proto-oncogene with MEN2A or MEN2B mutation.
    Oncogene 12, 481-487 (1996).
  • Asai, N., Iwashita, T., Matsuyama, M. and Takahashi, M.
    Mechanism of activation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations.
    Mol. Cell. Biol. 15, 1613-1619 (1995).
  • Takahashi, M.
    Oncogenic activation of the ret protooncogene in thyroid cancer.
    Crit. Rev. Oncog. 6, 35-46 (1995).
  • Tsuzuki, T., Takahashi, M., Asai, N., Iwashita, T., Matsuyama, M. and Asai, J.
    Spatial and temporal expression of the ret proto-oncogene product in embryonic, infant and adult rat tissues.
    Oncogene 10, 191-198 (1995).
  • Iwamoto, T., Taniguchi, M., Asai, N., Ohkusu, K., Nakashima, I. and Takahashi, M.
    cDNA cloning of mouse ret proto-oncogene and its sequence similarity to the cadherin superfamily.
    Oncogene 8, 1087-1091 (1993).
  • Takahashi, M., Asai, N., Iwashita, T., Isomura, T., Miyazaki, K. and Matsuyama, M.
    Characterization of the ret proto-oncogene products expressed in mouse L cells.
    Oncogene 8, 2925-2929 (1993).
  • Iwamoto, T., Takahashi, M., Ito, M., Hamatani, M., Ohbayashi, M., Wajjwalku, W., Isobe, K. and Nakashima I.
    Aberrant melanogenesis and melanocytic tumor development in transgenic mice that carry a metallothionein/ret fusion gene.
    EMBO J. 10, 3167-3175 (1991).
  • Takahashi, M., Buma, Y. and Taniguchi, M.
    Identification of the ret proto-oncogene products in neuroblastoma and leukemia cells.
    Oncogene 6, 297-301 (1991).
  • Takahashi, M., Buma, Y., Iwamoto, T., Inaguma, Y., Ikeda, H. and Hiai, H.
    Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domain.
    Oncogene 3, 571-578 (1988).
  • Takahashi, M., Inaguma, Y., Hiai, H. and Hirose, F.
    Developmentally regulated expression of a human finger-containing gene encoded by the 5’ half of the ret proto-oncogene.
    Mol. Cell. Biol. 7, 1853-1856 (1988).
  • Takahashi, M. and Cooper, G. M.
    ret transforming gene encodes a fusion protein homologous to tyrosine kinases.
    Mol. Cell. Biol. 7, 1378-1385 (1987).
  • Takahashi, M., Ritz, J. and Cooper, G.M.
    Activation of a novel human transforming gene, ret, by DNA rearrangement.
    Cell 42, 581-588 (1985).