Roles of TGF-β signaling in cancer progression

• 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
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2008: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 実験腫瘍学 / TGF-β / EMT / 上皮間葉転換 / 筋線維芽細胞 / FGF-2 / アイソフォームスイッチ / 上皮間葉移行 / Snail / Ras / 癌微小環境

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] TGF-βregulates isoform switching of FGF receptors and epithelial-mesenchymal transition. (2011)
  • Author(s): Shirakihara T, etal
  • Journal Title: EMBO J Volume: 30 Pages: 783-795
  • Peer Reviewed
• [Journal Article] Transforming Grawth Factor-βsignaling and Epithelial Mesenchymal Transition (2011)
  • Author(s): Saitoh.M
  • Journal Title: J. Oral Biosci. Volume: 53 Pages: 57-64
  • 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: 15737-15737
  • 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: 11404-11404
  • Peer Reviewed
• [Journal Article] Identification of a phosphorylation site in c-Ski as serine 515. (2010)
  • Author(s): Nagata M, etal
  • Journal Title: J.Siochem. Volume: 148 Pages: 423-427
  • Peer Reviewed
• [Journal Article] Arkadia complexes with clathrin adaptor AP2 and regulates EGF signaling (2010)
  • Author(s): Mizutani A, etal
  • Journal Title: J.Biochem. Volume: 148 Pages: 733-741
  • 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] Role of Ras signaling in the Induction of Snail by TGF-β (2009)
  • Author(s): Horiguchi K., etal
  • Journal Title: Journal of Biological Chemistry 284 Pages: 245-253
  • Peer Reviewed
• [Journal Article] Regulation of the stability of cell surface E-cadherin by the proteasome (2009)
  • Author(s): Saitoh M., etal
  • Journal Title: Biochemical and Biophysical Research Cmmunication 381 Pages: 560-565
  • Peer Reviewed
• [Journal Article] TTF-1 inhibits TGF-β-mediated EMT in lung adenocarcinoma cells (2009)
  • Author(s): Saito RA., etal
  • Journal Title: Cancer Research 69 Pages: 2783-2791
  • 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
• [Journal Article] Smurf2 induccs ubiquitil-dependent degradation of Smurfl to prevent migration of breast cancer cells. (2008)
  • Author(s): Fukunaga E. etal
  • Journal Title: J. Biol. Chem 284 Pages: 245-253
  • Peer Reviewed
• [Presentation] TGF-βswitches isoform of FGF receptors and regulates EMT of cancer-associated epithelial cells (2011)
  • Author(s): Masao Saitoh
  • Organizer: Keystone meeting
  • Place of Presentation: Bancouver, Canada
  • Year and Date: 2011-01-23
• [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] TGF-b signaling & EMT in cancer progression (2010)
  • Author(s): 齋藤正夫
  • Organizer: 日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] FGF-2 accelerates TGF-β-induced EMT and promotes invasion of cancer cells (2010)
  • Author(s): Masao Saitoh
  • Organizer: AACR
  • Place of Presentation: Washington, USA
  • Year and Date: 2010-03-01
• [Presentation] FGF-2 accelerates TGF-β-induced EMT and promotes invasion of cancer cells (2009)
  • Author(s): 齋藤正夫
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [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
• [Presentation] Molecular mechanism of TGF-β-induced EMT (2009)
  • Author(s): 齋藤正夫
  • Organizer: 日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Presentation] 癌細胞浸潤過程におけるEMTの役割 (2009)
  • Author(s): 齋藤正夫
  • Organizer: 歯科基礎医学会総会
  • Place of Presentation: 新潟
  • Year and Date: 2009-09-09
• [Presentation] TGF-βによるSnailの発現調節に対するRasシグナルの関与 (2008)
  • Author(s): 堀口華奈
  • Organizer: 分子生物学会
  • Place of Presentation: 兵庫県、神戸市、国際会議揚
  • Year and Date: 2008-12-12