Identification of Smad cofactors involved in tumor progression

• Project/Area Number: 16H05150
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: University of Yamanashi
• Principal Investigator: MIYAZAWA KEIJI 山梨大学, 大学院総合研究部, 教授 (40209896)
• Research Collaborator: ITOH yuka ; MOTIZUKI mitsuyoshi ; MIYAKE kunio
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: シグナル伝達 / TGF-β / Smad / 転写活性化 / がん / 癌

Outline of Final Research Achievements

In the present study, we worked on Smad cofactors in cancer cells, which enable a wide variety of cell responses induced by TGF-β. We identified Olig1 as a Smad cofactor involved in anti-apoptotic function of TGF-β in murine breast cancer cells. We also developed a strategy to screen Smad cofactors that operate in cancer cells and identified two novel Smad cofactors. Furthermore, we found minimal requirements for transcription activation by cooperation of Smad and Smad cofactors.

Academic Significance and Societal Importance of the Research Achievements

TGF-βの多様な作用の一部のみを選択的に抑制する次世代のTGF-β阻害薬開発のためには、個々の作用に密接に結びついたSmad cofactorを同定し、その機能の発現メカニズムを明らかにする必要がある。本研究では新規Smad cofactorの探索法を開発するとともに、Smad cofactorの作用を効率的にブロックする手法を開発するための基礎として、SmadとSmad cofactorによる協調的な転写活性化の必要条件を明らかにした。

Research Products

• [Presentation] Crucial role of Smad3 in protumorigenic TGFβ signaling (2019)
  • Author(s): Keiji Miyazawa
  • Organizer: STINT Special Symposium on the Sweden-Japan 150 Anniversary Grant "Pro-tumorigenic TGFβ signaling"
  • Int'l Joint Research / Invited
• [Presentation] TGF-βによる転写制御とSmad結合配列の多様性 (2018)
  • Author(s): 伊藤友香、宮澤恵二
  • Organizer: 日本生化学会
  • Invited
• [Presentation] Analysis of DNA binding properties of Smad proteins by cyclic amplification of selective target method (2018)
  • Author(s): Yuka Itoh, Kunio Miyake, Masao Saitoh, Keiji Miyazawa
  • Organizer: 12th International BMP Conference
  • Int'l Joint Research
• [Presentation] Canonincal and non-canonical Smad signaling pathways (2017)
  • Author(s): 宮澤恵二
  • Organizer: ConBio2017 ワークショップ
  • Place of Presentation: 神戸ポートピアホテル（神戸市中央区）
  • Year and Date: 2017-12-08
  • Invited
• [Presentation] Heterogeneity of Smad-Smad cofactor complexes and context-dependent TGF-β signaling (2017)
  • Author(s): Keiji Miyazawa
  • Organizer: TGF-β meeting
  • Place of Presentation: Uppsala, Sweden
  • Year and Date: 2017-09-02
  • Int'l Joint Research
• [Presentation] Heterogeneity of Mad-Smad cofactor complex and context-dependent TGF-β signaling (2017)
  • Author(s): Keiji Miyazawa
  • Organizer: TGF-β meeting
  • Int'l Joint Research
• [Presentation] Canonical and non-canonical Smad signaling pathways (2017)
  • Author(s): 宮澤恵二
  • Organizer: COnBIo2017 ワークショップ
  • Invited
• [Presentation] Smad binding proteins in context-dependent TGF-β signaling (2016)
  • Author(s): Keiji Miyazawa
  • Organizer: 日本癌学会第75回学術集会 コアシンポジウム
  • Place of Presentation: パシフィコ横浜（横浜市西区）
  • Year and Date: 2016-10-07
  • Invited
• [Presentation] Smad-dependent signaling and Smad binding cofactors (2016)
  • Author(s): Keiji Miyazawa
  • Organizer: TGF-β meeting
  • Place of Presentation: Leiden, Nederlands
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Remarks] 山梨大学医学部生化学講座第２教室ホームページ
  • URL: https://www.med.yamanashi.ac.jp/basic/bioche02/bioch2.html
• [Remarks] 山梨大学医学部生化学講座第２教室ホームページ
  • URL: http://www.med.yamanashi.ac.jp/basic/bioche02/