Study of the molecular mechanisms underlying endothelilal-to mesenchymal transition which promotes cancer progression

• Project/Area Number: 22590283
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: WATABE Tetsuro 東京大学, 大学院・医学系研究科, 准教授 (00334235)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 癌 / 血管新生 / シグナル伝達 / 血管

Research Abstract

Progression of cancer is induced by cancer associated fibroblasts (CAF). Recent reports have indicated that CAF is derived from tumor endothelial cells through endothelial-to-mesenchymal transition (EndMT). In the present study, we studied the molecular mechanisms underlying EndMT. Using MS-1 endothelial cells, I have found that activation of MRTF-A transcription factor by Rho signals is necessary for TGF-β-induced EndMT. I also found that BMP-9 and FGF enhanced and suppressed the TGF-β-induced EndMT. These results suggest that signaling cascades mediated by multiple cytokines modulate the TGF-β-induced EndMT.

Research Products

• [Journal Article] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A (2012)
  • Author(s): Mihira H, Suzuki HI, Akatsu Y, Yoshimatsu Y, Igarashi T, Miyazono K, Watabe T.
  • Journal Title: Journal of Biochemistry Volume: 143 Pages: 199-206
  • NAID: 10031166053
  • Peer Reviewed
• [Journal Article] TGF-β-induced epithelial-mesenchymal transition of A549 lung adenocarcinoma cells is enhanced by pro-inflammatory cytokines derived from RAW 264.7 macrophage cells (2012)
  • Author(s): Kawata M, Koinuma D, Ogami T, Umezawa K, Iwata C, Watabe T, Miyazono K.
  • Journal Title: Journal of Biochemistry Volume: 151 Pages: 205-216
  • NAID: 10031166059
  • Peer Reviewed
• [Journal Article] TGF-β-induced epithelial-mesenchymal transition of A549 lung adenocarcinoma cells is enhanced by pro-inflammatory cytokines derived from RAW 264.7 macrophage cells. (2012)
  • Author(s): 2. Kawata M, Koinuma D, Ogami T, Umezawa K, Iwata C, Watabe T, Miyazono K.
  • Journal Title: Journal of Biochemistry Volume: 151 Issue: 2 Pages: 205-216
  • DOI: 10.1093/jb/mvr136
  • NAID: 10031166059
  • Peer Reviewed
• [Journal Article] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A (2012)
  • Author(s): Mihira H, Suzuki HI, Akatsu Y, Yoshimatsu Y, Igarashi T, Miyazono K, Watabe T
  • Journal Title: Journal of Biochemistry Volume: 151 Pages: 145-156
  • NAID: 10031166053
  • Peer Reviewed
• [Journal Article] BMP-9 induces proliferation of multiple types of endothelial cells in vitro and in vivo (2010)
  • Author(s): Suzuki Y, Ohga N, Morishita Y, Hida K, Miyazono K, Watabe T.
  • Journal Title: Journal of Cell Science Volume: 123 Pages: 1684-1692
  • Peer Reviewed
• [Presentation] Activation of Signaling and Transcriptional Networks during TGF-β-inducedEndothelial-to-Mesenchymal Transition(EndMT) (2012)
  • Author(s): Watabe T, Kokudo T, Mihira H, Yoshimatsu Y, Miyazono K.
  • Organizer: The 17th International Vascular Biology Meeting
  • Place of Presentation: Wiesbarden, Germany
• [Presentation] Activation of Signaling and Transcriptional Networks during TGF-β-induced Endothelial-to-Mesenchymal Transition (EndMT). (2012)
  • Author(s): Watabe T
  • Organizer: The 17th International Vascular Biology Meeting
  • Place of Presentation: Wiesbarden, Germany
• [Presentation] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A (2011)
  • Author(s): 渡部徹郎
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-13
• [Presentation] BMP9 induces proliferation of mouse embryonic stem cell-derived endothelial cells (2011)
  • Author(s): Watabe T, Suzuki Y, Yoshimatsu Y, Miyazono K.
  • Organizer: The 9th Annual Meeting of International Society for Stem Cell Research Meeting
  • Place of Presentation: Toronto, Canada
• [Presentation] Ets family members induce lymphangiogenesis via physical and functional interaction with Prox1 (2010)
  • Author(s): Watabe T, Yoshimatsu Y, Mihira H, Itoh T, Yuki K, Harada K, Iwata C, Yamazaki T, Morikawa M, Miyazono K.
  • Organizer: The 16th International Vascular BiologyMeeting
  • Place of Presentation: Los Angeles, U.S.A.