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PathologyTumor Pathology/Molecular Pathology

Introduction

Our department is responsible for education of pathology for medical students and is pursuing research in cancer and neurological disease. Our major research interests include (1) Roles of the RET proto-oncogene in cancer development and organogenesis, (2) Molecular mechanisms of cell motility mediated by Akt signaling and Girdin family proteins, (3) Roles of CD109 in cancer progression and (4) Roles of Meflin (ISLR), a newly identified marker for mesenchymal stem cells, in pathological fibrosis and cancer microenvironment.

Research Projects

(1) Roles of the RET proto-oncogene in cancer development and organogenesis
  The RET oncogene was identified by transfection of NIH3T3 cells (Takahashi et al. Cell 1985). The RET proto-oncogene encodes a receptor tyrosine kinase whose expression is detected in the nervous system and the embryonic urogenital system. Mutations in RET are responsible for the development of papillary thyroid cancer, lung adenocarcinoma, multiple endocrine neoplasia type 2 and Hirschsprung disease (Takahashi, Cytokine Growth Factor Rev, 2001). Our group has been studying the molecular mechanisms of these diseases caused by RET mutations.
  RET is activated by glial cell line-derived neurotrophic factor (GDNF) which binds to GDNF family receptor ??(Treanor et al, Nature 1996)??GDNF-GFR?-RET signaling is essential for the development of the enteric nervous system, renal organogenesis and spermatogenesis. Using several Ret mutant mice, we are studying the roles of RET signaling in organogenesis.

(2) Molecular mechanisms of cell motility mediated by Akt signaling and Girdin family proteins
  It is known that Akt signaling plays an important role in the motility of various types of cells. We identified a new Akt substrate and an actin-binding protein Girdin using an yeast two-hybrid screening (Enomoto et al. Dev Cell 2005). In response to growth factor stimulation, Girdin is phosphorylated at serine 1416 by Akt and accumulated at the leading edge of migrating cells. When Girdin expression is knock-downed by siRNA, lamellipodia formation at the leading edge is largely impaired, resulting in the decrease of cell migration. Actually, Girdin is necessary for the motility of cancer cells, endothelial cells and neuronal cells. Girdin KO mice showed the impaired vascular development in the retina and brain, the impaired chain migration of neuroblasts in rostral migratory stream and the abnormal architecture in the dentate gyrus (Kitamura et al, Nat Cell Biol, 2008; Jiang et al, Cancer Res, 2008; Enomoto et al, Neuron 2009; Wang et al, J Neurosci, 2011). Our group is studying the precise mechanisms of cell motility via Girdin function, particularly about how Girdin regulates the actin reorganization at lamellipodia.

(3) Roles of CD109 in cancer progression
  CD109 is a glycosylphosphatidylinositol-anchored cell surface protein. We identified CD109 as a protein induced by activation of RET tyrosine kinase. CD109 expression was detected in various cancer cells including squamous cell carcinoma, glioblastoma and adenocarcinoma (Hashimoto et al, Oncogene, 2004). Using CD109-deficient mice, we showed that CD109 expression promotes tumor growth and progression (Sunagawa et al, Oncotarget, 2016; Shiraki et al, J Pathol, 2017). In particular, CD109 was highly expressed in brain tumor stem cells (BTSC) in the perivascular region, suggesting that CD109 becomes a potential target for cancer therapy. We are now developing monoclonal antibodies against CD109 and investigating their efficacy on cancer therapy.
  CD109 is known to negatively regulate TGF-??signaling (Hagiwara et al, Oncogene, 2010) and positively regulate EGF signaling (Zhang et al, BBRC, 2015). It is also our interest to study the mechanisms on how CD109 regulates these signaling pathways and its biological significance.

(4) Roles of Meflin (ISLR), a newly identified marker for mesenchymal stem cells (MSC), in pathological fibrosis and cancer microenvironment.
  Like CD109, Meflin, which is encoded by ISLR gene, is a glycosylphosphatidylinositol-anchored cell surface protein. Meflin is expressed in cultured MSCs as well as stromal cells throughout the bone marrow, pericytes and perivascular cells in multiple organs but not other types of cells. Meflin maintains the undifferentiated state of cultured MSCs and is downregulated upon their differentiation (Maeda et al, Sci Rep, 2016). Thus, we suppose that Meflin is a new useful marker for MSCs. In addition, we recently found that a portion of cancer-associated fibroblasts (CAF) expressed Meflin. Interestingly, Meflin-high CAF and ?low CAF are ?SMA-low and ?high CAF, respectively. The aim of this project is to elucidate the functional difference of Meflin-high or ?low fibroblasts in cancer microenvironment and in pathological fibrosis.

Faculty Members

FacultyPositionDepartment
Masahide takahashi Honorary professor
Atsushi enomoto Professor
Yukihiro shiraki Assistant Professor
Shinji mii Designated Assistant Professor

Bibliography

  • 2018
    1. 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 and Takahashi M.Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex.PLoS Biol. 2018 Mar 14;16(3):e2005090.
    2. Maegawa T, Miyasaka Y, Kobayashi M, Babaya N, Ikegami H, Horio F, Takahashi M. and Ohno T.Congenic mapping and candidate gene analysis for streptozotocin-induced diabetes susceptibility locus on mouse chromosome 11.Mamm Genome (2018) in press
    3. Ushida K, Asai N, Uchiyama K, Enomoto A and 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) in press.
    4. 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 and Sugimura Y.Critical role of rabphilin-3A in the pathophysiology of experimental lymphocytic neurohypophysitis.J Pathol. (2018) in press
    5. 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. 109: 141-153 (2018)
  • 2017
    1. 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).
    2. 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).
    3. 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).
    4. 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) .
  • 2016
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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) .
    6. 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).
    7. 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).
    8. 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).
    9. 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).
  • 2015
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
    6. 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).
    7. 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).
    8. 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-neurohypophysitisJ. Clin. Endocrinol .Metab. 100: E946-54 (2015).
    9. 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).
    10. 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)
  • 2014
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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)
    6. 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 cellsCancer Sci. 105:545-552 (2014).
    7. 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).
    8. 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).
    9. 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
    10. 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).
    11. 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).
    12. 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).
    13. 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).
  • 2013
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
    6. 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).
    7. 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).
  • 2012
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
    6. 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).
    7. 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).
    8. 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).
    9. 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).
    10. 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).
    11. 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).
    12. 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).
    13. 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).
  • 2011
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
    6. 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).
    7. 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).
    8. 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).
    9. 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).
    10. 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 miceDev. Biol.349: 160-168 (2011).
    11. 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).
  • 2010
    1. 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).
    2. 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.
    3. c-Ret-mediated hearing loss in mice with Hirschsprung disease.Proc. Natl. Acad. Sci. USA. 107: 13051-13056 (2010).
    4. 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)
    5. 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).
    6. 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).
    7. 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).
    8. 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).
    9. 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).
  • 2009
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
    6. 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, FRet-dependent cell rearrangements in the Wolffian duct epithelium initiate ureteric bud morphogenesis.Dev. Cell 17: 199-209 (2009).
    7. 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/Rac1FEBS Lett. 583: 2457-2463 (2009).
    8. 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).
    9. 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).
  • 2008
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
    6. 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).
    7. 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).
  • 2007
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
    6. 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).
    7. 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 cellsPathol. Int. 57: 245-250 (2007).
    8. 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).
    9. 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).
  • 2006
    1. 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).
    2. Murakumo, Y., Jijiwa, M., Asai, N., Ichihara, M., and Takahashi, M.RET and neuroendocrine tumors.Pituitary 9: 179-192 (2006).
    3. 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).
    4. 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).
    5. 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).
    6. 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).
    7. 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).
    8. 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).
  • 2005
    1. 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 cervixPathol Int. 55: 165-169 (2005).
    2. 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).
    3. 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).
    4. 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.
    5. 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.
    6. 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.
    7. 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.
  • 2004
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
    6. 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).
    7. Ichihara, M., Murakumo, Y., and Takahashi, M.RET and neuroendocrine tumors.Cancer Lett. 204:197-211 (2004).
  • 2003
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
    6. 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).
    7. 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).
    8. 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).
    9. 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).
  • 2002
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
  • 2001
    1. 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).
    2. 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).
    3. Takahashi, M.The GDNF/RET signaling pathway and human diseases.Cysokine & Growth Factor Reviews 12: 361-373 (2001).
    4. 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).
    5. 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).
    6. 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).
    7. 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).
    8. 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).
  • 2000
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
  • 1999
    1. 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)
    2. 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).
    3. 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).
    4. 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).
    5. 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).
    6. 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).
    7. 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).
    8. 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).
    9. 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).
  • 1998
    1. 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).
    2. 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).
    3. 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).
    4. 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).
    5. 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).
  • 1997
    1. 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).
    2. 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).
    3. 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).
  • 1996
    1. 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).
    2. 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).
    3. 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).
    4. 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).
  • 1995
    1. 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).
    2. Takahashi, M.Oncogenic activation of the ret protooncogene in thyroid cancer.Crit. Rev. Oncog. 6, 35-46 (1995).
    3. 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).
  • 1993
    1. 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).
    2. 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).
  • 1991
    1. 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).
    2. Takahashi, M., Buma, Y. and Taniguchi, M.Identification of the ret proto-oncogene products in neuroblastoma and leukemia cells.Oncogene 6, 297-301 (1991).
  • 1988
    1. 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).
    2. 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).
  • 1987
    1. Takahashi, M. and Cooper, G. M.ret transforming gene encodes a fusion protein homologous to tyrosine kinases.Mol. Cell. Biol. 7, 1378-1385 (1987).
  • 1985
    1. Takahashi, M., Ritz, J. and Cooper, G.M.Activation of a novel human transforming gene, ret, by DNA rearrangement.Cell 42, 581-588 (1985).