Roles of TGF-β signaling in cancer progression

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390476
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: The University of Tokyo
• Principal Investigator: SAITOH Masao The University of Tokyo, 大学院・医学工学総合研究部, 准教授 (90345041)
• Project Period (FY): 2008 – 2010
• Keywords: 実験腫瘍学

Research Abstract

We found that transforming growth factor (TGF)-b induced EMT and that long-term exposure to TGF-b elicited the epithelial-myofibroblastic transition (EMyoT) by inactivating the MEK-Erk pathway. During the EMT process, TGF-b induced isoform switching of fibroblast growth factor (FGF) receptors, causing the cells to become sensitive to FGF-2. The addition of FGF-2 to TGF-b-treated cells perturbed EMyoT by reactivating the MEK-Erk pathway and subsequently enhanced EMT.

Research Products

• [Journal Article] TGF-β regulates isoform switching of FGF receptors and epithelial-mesenchymal transition. (2011)
  • Author(s): Shirakihara T, Horiguchi K, Miyazawa K, Ehata S, Shibata T, Morita I, Miyazono K, Saitoh M.
  • Journal Title: EMBO J. 30 Pages: 783-795
  • Peer Reviewed
• [Journal Article] Arkadia complexes with clathrin adaptor AP2 and regulates EGF signalling. (2010)
  • Author(s): Mizutani A, Saitoh M, Imamura T, Miyazawa K, Miyazono K.
  • Journal Title: J.Biochem. 148 Pages: 733-741
  • Peer Reviewed
• [Journal Article] Miyazono K, Miyazawa K Identification of a phosphorylation site in c-Ski as serine 515. (2010)
  • Author(s): Nagata M, Nagata S, Yuki K, Isogaya K, Saitoh M
  • Journal Title: J.Biochem. 148(4) Pages: 423-427
  • Peer Reviewed
• [Journal Article] RB1CC1 together with RB1 and p53 predicts long-term survival in japanese breast cancer patients. (2010)
  • Author(s): Chano T, Ikebuchi K, Tomita Y, Jin Y, Inaji H, Ishitobi M, Teramoto K, Ochi Y, Tameno H, Nishimura I, Minami K, Inoue H, Isono T, Saitoh M, Shimada T, Hisa Y, Okabe H.
  • Journal Title: PLoS One. 5 Pages: 15737
  • Peer Reviewed
• [Journal Article] RB1CC1 activates RB1 pathway and inhibits proliferation and cologenic survival in human cancer. (2010)
  • Author(s): Chano T, Ikebuchi K, Ochi Y, Tameno H, Tomita Y, Jin Y, Inaji H, Ishitobi M, Teramoto K, Nishimura I, Minami K, Inoue H, Isono T, Saitoh M, Shimada T, Hisa Y, Okabe H.
  • Journal Title: PLoS One. 5 Pages: 11404
  • Peer Reviewed
• [Journal Article] Thyroid transcription factor-1 inhibits transforming growth factor-beta-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells. (2009)
  • Author(s): Saito RA, Watabe T, Horiguchi K, Kohyama T, Saitoh M, Nagase T, Miyazono K.
  • Journal Title: Cancer Res. 69 Pages: 2783-2791
  • Peer Reviewed
• [Journal Article] Regulation of the stability of cell surface E-cadherin by the proteasome. (2009)
  • Author(s): Saitoh M, Shirakihara T, Miyazono K.
  • Journal Title: Biochem.Biophys.Res.Commun. 381 Pages: 560-565
  • Peer Reviewed
• [Journal Article] Dp63 -dependent expression of Id-3 distinctively suppresses the invasiveness of human squamous cell carcinoma with epithelial-to-mesenchymal transition. (2009)
  • Author(s): Higashikawa K, Yoneda1S, Tobiume K, Saitoh M, Taki M, Mitani Y, Shigeishi H, Ono S, Kamata N.
  • Journal Title: Int J.Cancer 124 Pages: 2837-2844
  • Peer Reviewed
• [Journal Article] Pin1 downregulates TGF-beta signaling by inducing degradation of Smad proteins. (2009)
  • Author(s): Nakano A, Koinuma D, Miyazawa K, Uchida T, Saitoh M, Kawabata M, Hanai JI, Akiyama H, Abe M, Miyazono K, Matsumoto T, Imamura T.
  • Journal Title: J.Biol.Chem. 284 Pages: 6109-6115
  • Peer Reviewed
• [Journal Article] Role of Ras signaling in the induction of snail by TGF-b. (2009)
  • Author(s): Horiguchi K, Shirakihara T, Nakano A, Imamura T, Miyazono K, Saitoh M.
  • Journal Title: J.Biol.Chem 284 Pages: 245-253
  • Peer Reviewed
• [Journal Article] Smurf2 induces ubiquitin-dependent degradation of Smurf1 to prevent migration of breast cancer cells. (2008)
  • Author(s): Fukunaga E, Inoue Y, Komiya S, Horiguchi K, Goto K, Saitoh M, Miyazawa K, Koinuma D, Hanyu A, Imamura T.
  • Journal Title: J.Biol.Chem 283 Pages: 35660-35667
  • Peer Reviewed
• [Presentation] TGF-b signaling and EMT in cancer progression (2010)
  • Author(s): 齋藤正夫
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] FGF-2 accelerate TGF-b-induced EMT and promotes invasion of cancer cells (2009)
  • Author(s): Masao Saitoh, Takuya Shirakihara, Kana Horiguchi, Kohei Miyazono
  • Organizer: 第32回日本分子生物学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] molecular mechanism of TGF-b-induced EMT (2009)
  • Author(s): 齋藤正夫
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03