Inhibition of the maintenance of stemness of glioma initiating cells for clinical applications

• Project/Area Number: 26830067
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kinki University (2015); The University of Tokyo (2014)
• Principal Investigator: KOMURO Akiyoshi 近畿大学, 医学部, 助教 (50512274)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: がん幹細胞 / 脳腫瘍 / BMP / 融合遺伝子 / 膠芽腫 / 脳腫瘍幹細胞 / 骨形成因子 / BMP4

Outline of Final Research Achievements

We attempted to enhance Bone Morphogenetic Protein (BMP) signal in glioma initiating-cells (GICs) by using of siRNA for Smad6 which is the intracellular inhibitor of BMP signal, we observed that BMP4+siSmad6 dramatically inhibited the maintenance of stemness of GICs. Furthermore, we identified several target genes of BMP4+siSmad6 that had the inhibitory effects of the maintenance of stemness of GICs. Additionally, we discovered several novel fusion genes in GICs by using RNA-Seq of this study, and we found that one of fusion genes identified had the transforming potential and high tumor-forming capacity.

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
• [Journal Article] Bone morphogenetic protein signaling mediated by ALK-2 and DLX2 regulates apoptosis in glioma-initiating cells (2017)
  • Author(s): Raja E, Komuro A, Tanabe R, Sakai S, Ino Y, Saito N, Todo T, Morikawa M, Aburatani H, Koinuma D, Iwata C, Miyazono K.
  • Journal Title: Oncogene Volume: 36 Issue: 35 Pages: 4963-4974
  • DOI: 10.1038/onc.2017.112
  • Peer Reviewed / Open Access
• [Presentation] 膠芽腫における新規融合遺伝子 HMGA2-EGFR の同定 (2015)
  • Author(s): 古室 暁義, 岩田 要, 曽田 学, 磯谷 一暢, 鈴木 啓道, Melissa Ranjit, 稲生 靖, 藤堂 具紀, 油谷 浩幸, 夏目 敦至, 武笠 晃丈, 斉藤 延人, 間野 博行, 宮園 浩平, 鯉沼 代造
  • Organizer: 分子生物学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] Identification of a novel fusion gene, HMGA2-EGFR in glioblastoma (2015)
  • Author(s): Akiyoshi Komuro, Caname Iwata, Manabu Soda, Kazunobu Isogaya, Yasushi Ino, Tomoki Todo, Hiroyuki Aburatani, Atsushi Natsume, Akitake Mukasa, Nobuhito Saito, Hiroyuki Mano, Kohei Miyazono, Daizo Koinuma
  • Organizer: Joint international symposium on TGF-β family and cancer Signal network in tumor microenvironment
  • Place of Presentation: International congress center ‘Epochal Tsukuba’ (Tsukuba Ibaraki)
  • Year and Date: 2015-01-12 – 2015-01-13