A potential role of mitochondria-mediated signaling in induction of malignancy and stemness by TGF.

• Project/Area Number: 21570205
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Showa University
• Principal Investigator: SHIBANUMA Motoko 昭和大学, 薬学部, 教授 (60245876)
• Co-Investigator(Kenkyū-buntansha): MORI Kazunori 昭和大学, 薬学部, 助教 (60349040) ; ISHIKAWA Fumihiro 昭和大学, 薬学部, 助教 (60515667)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ミトコンドリア / CREB / HMGA2 / CHOP-10 / TGFβ / 膜電位 / 活性酸素 / チオレドキシン / プロテインキチーゼC / MMP9

Research Abstract

cAMP-responsive element-binding protein(CREB) was found to be activated and cause morphological disruption of epithelial cells under mitochondrial dysfunction. Of note, activated CREB upregulated HMGA2, resulting in activation of epithelial-mesenchymal transition(EMT) program and modulation of integrin. 1 expression. Overall, the results suggest that mitochondrial dysfunction potentially mediates TGF-.-induced malignancy and contributes to neoplastic transformation of epithelial cells.

Research Products

• [Journal Article] Importance of mitochondrial dysfunction in oxidative stress responses : A comparative study of gene expression profiles (2011)
  • Author(s): Shibanuma, M., Inoue, A., Ushida, K., Uchida, T., Ishikawa, F., Mori, K., and Nose, K.
  • Journal Title: Free Radic. Res Volume: 45 Pages: 672-680
• [Journal Article] A mobile molecular scaffold regulating the anchorage dependence of cell growth (2011)
  • Author(s): Shibanuma, M., et.al.
  • Journal Title: Int J.Cell Biol. Volume: (in press) Pages: 1-8
  • DOI: 10.1155/2012/426138
  • Peer Reviewed
• [Journal Article] Importance of mitochondrial dysfunction in oxidative stress responses : A comparative study of gene expression profiles (2011)
  • Author(s): Shibanuma, M., et.al.
  • Journal Title: Free Radic.Res. Volume: 45 Pages: 672-680
  • Peer Reviewed
• [Journal Article] Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodering (2011)
  • Author(s): Kim-Kaneyama, J.-R., et.al.
  • Journal Title: J.Mol.Cell.Cardiol. Volume: 50 Pages: 77-86
  • Peer Reviewed
• [Journal Article] Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodering. (2011)
  • Author(s): Jon-ri Kim-Kaneyama, et.al.
  • Journal Title: J.Mol.Cell.Cardiol. Volume: 50 Pages: 77-86
  • Peer Reviewed
• [Journal Article] Importance of mitochondrial dysfunction in oxidative stress responses : A comparative study of gene expression Profiles. (2011)
  • Author(s): Motoko Shibanuma, et.al.
  • Journal Title: Free Radic.Res. Volume: 45 Pages: 672-680
  • Peer Reviewed
• [Journal Article] Transcriptional induction of MMP-10 by TGF-., mediated by activation of MEF2A and down-regulation of class IIa HDACs (2010)
  • Author(s): Ishikawa, F., Miyoshi, H., Nose, K., and Shibanuma, M.
  • Journal Title: Oncogene Volume: 29 Pages: 909-919
• [Journal Article] TGF-βによる細胞内レドックス制御とミトコンドリア (2010)
  • Author(s): 柴沼質子
  • Journal Title: 医学のあゆみ Volume: 234 Pages: 906-910
• [Journal Article] Transcriptional induction of MMP-10 by TGF-β, mediated by activation of MEF2A and downregulation class lla HDACs. (2010)
  • Author(s): Ishikawa, F., Miyoshi, H., Nose, K., Shibanuma, M.
  • Journal Title: Oncogene 29 Pages: 909-919
  • Peer Reviewed
• [Journal Article] Gene expression profiling identifies a role for CHOP-10 during inhibition of the mitochondrial respiratory chain (2009)
  • Author(s): Ishikawa, F., Akimoto, T., Yamamoto, H., Araki, Y., Yoshie, T., Mori, K., Hayashi, H., Nose, K., and Shibanuma, M.
  • Journal Title: J. Biochem Volume: 146 Pages: 123-132
• [Journal Article] Competitive nuclear export of cyclin D1 and Hic-5 regulates anchorage-dependence of cell growth and survival (2009)
  • Author(s): Mori, K., Hirao, E., Toya, Y., Oshima, Y., Ishikawa, F., Nose, K., and Shibanuma, M.
  • Journal Title: Mol. Biol Cell Volume: 20 Pages: 218-232
• [Journal Article] HIC-5 : A mobile molecular scaffold regulating the anchorage dependence of cell growth
  • Author(s): Shibanuma, M., Mori, K., and Nose, K.
  • Journal Title: Int J. Cell Biol Volume: (in press)
• [Presentation] Phenotypic disruption of mammary epithelial cells caused by mitochondrial dysfunction and the underlying mechanisms (2012)
  • Author(s): Shibanuma, M., Mori, K., Ishikawa, F.
  • Organizer: Keystone Symposia
  • Place of Presentation: Banff, Albert, Canada
• [Presentation] Phenotypic disruption of mammary epithelial cells caused by mitochondrial dysfunction and the underlying Mechanisms (2012)
  • Author(s): Shibanuma, M., Mori, K., Ishikawa, F.
  • Organizer: Keystone Symposia
  • Place of Presentation: Banff, Albert, Canada
• [Presentation] Phenotypic disruption of mammary epithelial cells caused by mitochondrial dysfunction and the underlying mechanisms (2011)
  • Author(s): Shibanuma, M., Mori, K., Ishikawa, F.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] ミトコンドリア機能不全によるEMTプログラムの活性化と上皮形質の破綻 (2011)
  • Author(s): 柴沼質子、森一憲、石川文博
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 細胞接着斑蛋白質Hic-5によるがん細胞の足場非依存性増殖/造腫瘍能の抑制性制御 (2011)
  • Author(s): 森一憲、石川文博、柴沼質子
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Mitochondria-mediated signaling cascade plays a role in the regulation of gene expression by TGF-β (2010)
  • Author(s): Motoko Shibanuma, et.al.
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] 接着喪失により誘導されるapoptosis関連遺伝子の検索と活性酸素種の関与 (2010)
  • Author(s): 牛田喬太, 他
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] ミトコンドリア特異的転写因子Tfam発現抑制による腫瘍の転移能抑制の可能性 (2010)
  • Author(s): 内田徹, 他
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] 細胞接着異常シグナルとしての活性酸素種、及びp21Cip1、細胞接着斑蛋白質Hic-5による足場依存性細胞増殖/生存制御 (2010)
  • Author(s): 森一憲, 他
  • Organizer: 第69回日本癌学会学術大会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] ミトコンドリア機能不全により誘導される上皮細胞形質の変化 (2010)
  • Author(s): 石川文博, 他
  • Organizer: 第69回日本癌学会学術大会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] Mitochondria-mediated signaling cascade plays a role in the regulation of gene expression by TGF (2010)
  • Author(s): Shibanuma, M., Kaneko, E., Sugimoto, T., Wakamatsu, M., Mori, K., Ishikawa, F.
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] ミトコンドリア特異的転写因子TFAM発現抑制による腫瘍の転移能抑制の可能性 (2010)
  • Author(s): 内田徹、石川文博、森一憲、柴沼質子
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] ミトコンドリア機能不全により誘導される上皮細胞形質の変化 (2010)
  • Author(s): 石川文博、森一憲、柴沼質子
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] ミトコンドリア由来ROSによるTGFβ遺伝子発現の抑制的制御機構の存在について (2009)
  • Author(s): 石川文博, 金子瑛美, 柴沼質子
  • Organizer: 第32回 日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] Transcriptional induction of MMP10 by TGF. mediated by MEF2 and class IIa HDACs (2009)
  • Author(s): Ishikawa, F., Kaneko, E., Yoshie, T., Nose, K., Shibanuma, M.
  • Organizer: Keystone Symposia
  • Place of Presentation: Vancouver, British Columbia, Canada
  • Year and Date: 2009-03-17
• [Presentation] ミトコンドリア由来ROSによるTGFβ遺伝子発現の抑制的制御機構の存在について (2009)
  • Author(s): 石川文博、金子瑛美、柴沼質子
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Remarks]
• [Remarks]
  • URL: http://www10.showa-u.ac.jp/~cancer/publication%202011.htm