Roles of the novel Akt substrate Girdin and its family of proteins in development and tumor protression

• Project/Area Number: 18689904
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Nagoya University
• Principal Investigator: ENOMOTO Atsushi Nagoya University, 高等研究院, 特任講師 (20432255)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥26,780,000 (Direct Cost: ¥22,100,000、Indirect Cost: ¥4,680,000); Fiscal Year 2008: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2007: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000); Fiscal Year 2006: ¥6,500,000 (Direct Cost: ¥6,500,000)
• Keywords: がん / Akt / 細胞骨格 / 浸潤 / Wnt / 血管新生 / Girdin / Daple / アクチン / 細胞浸潤 / 細胞運動

Research Abstract

Aktリン酸化酵素は細胞の増殖・分化にとって重要な分子であり、その異常活性化は細胞の癌化を誘導する。Aktが悪性腫瘍の浸潤や転移を促進するメカニズムの解明は治療法開発にも直結する重要課題である。近年私達が同定したAktの新規基質「Girdin」は細胞骨格の制御分子である。本研究では悪性腫瘍の進展におけるAkt/Girdinシグナル伝達系の意義を解明した。またGiridnおよびそのファミリー分子Dapleの遺伝子改変動物を作成し、生体内における各分子の意義について検討した。

Research Products

• [Journal Article] Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells (2009)
  • Author(s): Muteliefu G, Enomoto A, Jiang P, Takahashi M, Niwa T
  • Journal Title: Nephrol. Dial. Transplant. (in press)
  • Peer Reviewed
• [Journal Article] Indoxyl sulfate promotes proliferation of human aortic smooth muscle cells by inducing oxidative stress (2009)
  • Author(s): Muteliefu G, Enomoto A, Niwa T
  • Journal Title: J. Ren. Nutr. 19 Pages: 29-32
  • Peer Reviewed
• [Journal Article] Cell biology of the movement of breast cancer cells : Intracellular signalling and the actin cytoskeleton (2009)
  • Author(s): Ping Jiang
  • Journal Title: Cancer Letters (印刷中)
  • Peer Reviewed
• [Journal Article] lndoxyl sulfate promotes proliferation of human aortic smooth muscle cells by inducing oxidative stress (2009)
  • Author(s): Gulinuer Muteliefu
  • Journal Title: Journal of Renal Nutrition 19 Pages: 29-32
  • Peer Reviewed
• [Journal Article] Roles of induced expression of MAPK phosphatase-2 in tumor development in RET-MEN2A transgenic mice (2008)
  • Author(s): Hasegawa T, Enomoto A, Kato T, Kawai K, Miyamoto R, Jijiwa M, Ichihara M, Ishida M, Asai N, Murakumo Y, Ohara K, Niwa Y, Goto H, Takahashi M
  • Journal Title: Oncogene 27 Pages: 5684-95
  • Peer Reviewed
• [Journal Article] CD109 expression in basal-like breast carcinoma (2008)
  • Author(s): Hasegawa M, Moritani S, Murakumo Y, Sato T, Hagiwara S, Suzuki C, Mii S, Jijiwa M, Enomoto A, Asai N, Ichihara S, Takahashi M
  • Journal Title: Pathol Int. 58 Pages: 288-94
  • NAID: 10027376587
  • Peer Reviewed
• [Journal Article] GDNF-mediated signaling via RET tyrosine 1062 is essential for maintenance of spermatogonial stem cells (2008)
  • Author(s): Jijiwa M, Kawai K, Fukihara J, Nakamura A, Hasegawa M, Suzuki C, Sato T, Enomoto A, Asai N, Murakumo Y, Takahashi M
  • Journal Title: Genes Cells 13 Pages: 365-74
  • Peer Reviewed
• [Journal Article] An actin-binding protein Girdin regulates the motility of breast cancer cells (2008)
  • Author(s): Jiang, P., Enomoto, A., Jijiwa, M., Kato, T., Hasegawa, T., Ishida, M., Sato, T., Asai, N., Murakumo, Y., Takahashi, M.
  • Journal Title: Cancer Res. 68 Pages: 1310-8
  • Peer Reviewed
• [Journal Article] Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin (2008)
  • Author(s): Kitamura, T., Asai, N., Enomoto, A., Maeda, K., Kato, T., Ishida, M., Jiang, P., Watanabe, T., Usukura, J., Kondo, T., Costantini, F., Murohara, T., Takahashi, M.
  • Journal Title: Nat Cell Biol. 10 Pages: 329-37
  • Peer Reviewed
• [Journal Article] A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1 (2008)
  • Author(s): Suzuki, C., Murakumo, Y., Kawase, Y., Sato, T., Morinaga, T., Fukuda, N., Enomoto, A., Ichihara, M., Takahashi, M.
  • Journal Title: Biochem Biophys Res Commun. 366 Pages: 226-32
  • Peer Reviewed
• [Journal Article] 細胞運動におけるアクチン細胞骨格と膜輸送の強調 (2008)
  • Author(s): 榎本篤
  • Journal Title: 生化学 80 Pages: 233-240
• [Journal Article] An actin-binding protein Girdin regulates the motility of breast cancer cells (2008)
  • Author(s): Ping Jiang
  • Journal Title: Cancer Research 68 Pages: 1310-1318
  • Peer Reviewed
• [Journal Article] Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin (2008)
  • Author(s): Tomoya Kitamura
  • Journal Title: Nature Cell Biology 10 Pages: 329-337
  • Peer Reviewed
• [Journal Article] Roles of organic anion transporters in the progression of chronic renal failure (2007)
  • Author(s): Enomoto, A., Niwa, T.
  • Journal Title: Ther Apher Dial. 11 Suppl 1
  • Peer Reviewed
• [Journal Article] Nucleolin modulates the subcellular localization of GDNF-inducible zinc finger protein 1 and its roles in transcription and cell proliferation (2007)
  • Author(s): Dambara, A., Morinaga, T., Fukuda, N., Yamakawa, Y., Kato, T., Enomoto, A., Asai, N., Murakumo, Y., Matsuo, S., Takahashi, M.
  • Journal Title: Exp Cell Res. 313 Pages: 3755-66
  • Peer Reviewed
• [Journal Article] Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate (2007)
  • Author(s): Shin, H.J., Anzai, N., Enomoto, A., He, X., Kim, D.K., Endou, H., Kanai ,Y.
  • Journal Title: Hepatology 45 Pages: 1046-55
  • Peer Reviewed
• [Journal Article] Sprouty2 regulates growth and differentiation of human neuroblastoma cells through RET tyrosine kinase (2007)
  • Author(s): Ishida, M., Ichihara, M., Mii, S., Jijiwa, M., Asai, N., Enomoto, A., Kato, T., Majima, A., Ping, J., Murakumo, Y., Takahashi, M.
  • Journal Title: Cancer Sci. 98 Pages: 815-21
  • Peer Reviewed
• [Journal Article] Roles of organic anion transporters in the progression of chronic renal failure (2007)
  • Author(s): Atsushi Enomoto
  • Journal Title: Ther Apher Dial 11 Pages: 27-31
  • Peer Reviewed
• [Journal Article] Girdin, a novel actin-binding protein, and its family of proteins possess versatile functions in the Akt and Wnt signaling pathways. (2006)
  • Author(s): Atsushi Enomoto
  • Journal Title: Annals of New York Academy of Science 1086 Pages: 169-184
• [Journal Article] Targeted mutation of serine 697 in the Ret tyrosine kinase causes migration defect of enteric neural crest cells. (2006)
  • Author(s): Naoya Asai
  • Journal Title: Development 133・22 Pages: 4507-4516
• [Journal Article] Accumulation of indoxyl sulfate in OAT1/3-positive tubular cells in kidneys of patients with chronic renal failure. (2006)
  • Author(s): Kentaro Taki
  • Journal Title: Journal of Renal Nutrition 16・3 Pages: 199-203
• [Journal Article] Dok-4 regulates GDNF-dependent neurite outgrowth through downstream activation of Rap1 and mitogen-activated protein kinase. (2006)
  • Author(s): Mayumi Uchida
  • Journal Title: Journal of Cell Science 1・119 Pages: 3067-3077
• [Journal Article] RET receptor signaling : dysfunction in thyroid cancer and Hirschsprung's disease. (2006)
  • Author(s): Naoya Asai
  • Journal Title: Pathology International 56・4 Pages: 164-172
• [Presentation] Roles of Disrupted-In-Schizophrenia 1-Interacting Protein Girdin in Postnatal Development of the Dentate Gyrus (2008)
  • Author(s): Atsushi Enomoto
  • Organizer: The American Society of Cell Biology, 48 th Annual Meeting
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2008-12-17
• [Presentation] Roles of Disrupted-In-Schizophrenia 1-Interacting Protein Girdin in Postnatal Development of the Dentate Gyrus. The American Society of Cell Biology (2008)
  • Author(s): Enomoto, A., Asai, N., Taya, S., Tsuboi, D., Kuroda, S., Kaibuchi, K., Takahashi, M
  • Organizer: 48th Annual Meeting
  • Place of Presentation: San Francisco
  • Year and Date: 2008-12-13
• [Presentation] Characterization of the HDAC1 complex that regulates cancer cell sensitivity to oxidative stress. The American Society of Cell Biology (2008)
  • Author(s): Kato, T., Shimono, Y., Hasegawa, M., Jijiwa, M., Enomoto, A., Asai, N., Murakumo, Y., Takahashi, M.
  • Organizer: 48th Annual Meeting
  • Place of Presentation: San Francisco
  • Year and Date: 2008-12-13
• [Presentation] TBP-2の発現抑制に関わる転写複合体の解析 (2008)
  • Author(s): 加藤琢哉, 下野洋平, 榎本篤, 時々輪真由美, 村雲芳樹, 高橋雅英
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Aktの新基質であるGirdinは血管新生を制御する (2008)
  • Author(s): 北村トモヤ, 浅井直也, 榎本篤, 前田健吾, 加藤琢哉, 石田麻紀, 姜平, 渡辺崇, 臼倉治郎, Frank Costantini, 室原豊明, 高橋雅英
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 遺伝性の癌-その研究と臨床の最前線-RETチロシンキナーゼのシグナル伝達と発がん (2008)
  • Author(s): 高橋雅英, 長谷川太作, 榎本篤, 加藤琢哉, 石田麻紀, 時々輪真由美, 浅井直也, 村雲芳樹, 後藤秀実
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 神経細胞分化におけるアクチン結合蛋白質Girdin/Ccdc88aの機能解析 (2007)
  • Author(s): 榎本 篤
  • Organizer: 第30回日本分子生物学会年会BMB2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 神経細胞分化におけるアクチン結合蛋白質Girdin/Ccdc88aの機能解析 (2007)
  • Author(s): 榎本 篤, 浅井 直也, 高橋 雅英
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] Regulation of VEGF-Mediated Angiogenesis by the Akt/PKB Substrate Girdin (2007)
  • Author(s): Kitamura T, Asai N, Enomoto A, Maeda K, Jiang P, Watanabe T, Usukura J, Frank C, Murohara T, and Takahashi M
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] Sprouty2はRETチロシンキナーゼ下流シグナルによる神経芽細胞腫の増殖と分化を調節する (2007)
  • Author(s): 石田 麻紀, 市原 正智, 三井 伸二, 時々輪 真由美, 浅井 直也, 榎本 篤, 加藤 琢哉, 村雲 芳樹, 高橋 雅英
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] MAPK Phosphatase-2(MKP-2) Regulates Proliferation and Apoptosis of Breast Cancer Cells Derived from MEN2A Transgenic Mice (2007)
  • Author(s): 長谷川 太作, 榎本 篤, 川井 久美, 加藤琢哉, 時々輪 真由美, 浅井 直也, 村雲 芳樹, 後藤 秀実, 高橋 雅英
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] Regulation of cancer progression by the Akt/PKB substrate Girdin, a novel actin-binding protein (2007)
  • Author(s): 姜 平, 榎本 篤, 加藤 琢哉, 長谷川 太作, 佐藤 朋子, 時々輪 真由美, 浅井 直也, 村雲 芳樹, 高橋 雅英
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
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• [Patent(Industrial Property Rights)] アクチン結合タンパク質の細胞運動関連疾患への利用 (2006)
  • Inventor(s): 高橋雅英、榎本篤、室原豊明
  • Industrial Property Rights Holder: 平野眞一
  • Filing Date: 2006-11-10
  • Overseas