Elucidation of roles of small GTPase Ral and its negative regulator RalGAP in tumorigenesis, and cancer invasion and metastasis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25290041
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Tohoku University
• Principal Investigator: Horiuchi Hisanori 東北大学, 加齢医学研究所, 教授 (90291426)
• Co-Investigator(Renkei-kenkyūsha): OGAWA Osamu 京都大学, 医学研究科, 教授 (90260611) ; HIROYUKI Nishiyama 筑波大学, 人間総合科学研究科(系), 教授 (20324642) ; NAKASE Hiroshi 京都大学, 医学研究科, 講師 (60362498)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 腫瘍 / 低分子量GTP結合蛋白質 / Ral

Outline of Final Research Achievements

We have first identified negative regulators of small GTPases, Ral, that plays important roles in human tumorigenesis; RalGAP (JBC, 2009) and reported its important role in bladder cancer progression (Oncogene, 2013). We proceeded the investigation in this investigation as follows: (1) We found that Ral and RalGAP play an important role in inflammatory bowel disease and colitis-associated colon cancer formation. (2) We identified Ral-associated kinase and have been analyzing it. (3) We investigated the mechanism of reduced expression of RalGAP in bladder cancer cells and found an involvement of an epigenetic mechanism such as DNA methylation. (4) We have prepared its conditional KO mice in our laboratory. Currently, we are preparing its tissue specific KO mice. (5) We have summarized recent findings of Ral by focusing on RalGAP and published as a review article.

Free Research Field

生化学、腫瘍生物学、血栓止血学