Changes in the binding regions of Smads downstream of TGF-beta signaling in diffuse type gastric cancers

• Project/Area Number: 15K06831
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: The University of Tokyo
• Principal Investigator: Koinuma Daizo 東京大学, 大学院医学系研究科(医学部), 准教授 (80375071)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: シグナル伝達 / 癌 / 転写因子 / TGF-beta / ChIP-seq / スキルス胃がん / がん

Outline of Final Research Achievements

Cytokines of transfroming growth factor-beta (TGF-beta) play important roles in the pathogenesis of diffuse type gastric cancers. We previously reported that TGF-beta and the binding sites of its downstream Smad2/3 transcription factors are deferentially regulated in different types of the cells. We here analyzed our ChIP-seq data of Smad2/3 obtained from several diffuse type gastric cancer cell lines to reveal its regulatory mechanisms. Through comparison with the Smad2/3 binding data of the other cells, we identified a target gene of TGF-beta whose expression was deferentially correlated with the prognosis of patients with gastric cancer. We also found that this target gene regulated cellular motility, suggesting its roles in the progression of cancers.

Research Products

• [Journal Article] Identification of a novel fusion gene HMGA2-EGFR in glioblastoma (2017)
  • Author(s): Komuro Akiyoshi、Raja Erna、Iwata Caname、Soda Manabu、Isogaya Kazunobu、Yuki Keiko、Ino Yasushi、Morikawa Masato、Todo Tomoki、Aburatani Hiroyuki、Suzuki Hiromichi、Ranjit Melissa、Natsume Atsushi、Mukasa Akitake、Saito Nobuhito、Okada Hitoshi、Mano Hiroyuki、Miyazono Kohei、Koinuma Daizo
  • Journal Title: International Journal of Cancer Volume: 142 Issue: 8 Pages: 1627-1639
  • DOI: 10.1002/ijc.31179
  • Peer Reviewed / Open Access
• [Presentation] Integrated analysis of transcriptional regulation by Smads (2017)
  • Author(s): Daizo Koinuma
  • Organizer: TGF-beta meeting, Uppsala, Sweden
  • Int'l Joint Research
• [Presentation] Dynamics of chromatin accessibility during TGF-beta-induced EMT of Ras-transformed mammary gland epithelial cells (2015)
  • Author(s): Koinuma D, Arase M, Isogaya K, Nakaki R, Mizutani A, TsutsumiS, Aburatani H, Miyazono K
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Genome-wide profiling of TGF-beta-related transcription factor footprints (2015)
  • Author(s): Koinuma D
  • Organizer: TGF-beta meeting
  • Place of Presentation: Uppsala（Sweden）
  • Year and Date: 2015-08-19
  • Int'l Joint Research
• [Remarks] 東京大学大学院医学系研究科分子病理学分野
  • URL: http://beta-lab.umin.ac.jp/
• [Remarks] 東京大学大学院医学系研究科分子病理学ホームページ
  • URL: http://beta-lab.umin.ac.jp/