Elucidation of regulatory mechanism of diseases mediated by small GTP ase Ral

Research Project

Project/Area Number	16H05148
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Pathological medical chemistry
Research Institution	Tohoku University
Principal Investigator	Horiuchi Hisanori 東北大学, 加齢医学研究所, 教授 (90291426)
Research Collaborator	Ogawa Osamu 京都大学, 大学院医学研究科泌尿器科, 教授 Nakase Hiroshi 京都大学, 大学院医学研究科消化器内科講師, 講師
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000) Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000) Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000) Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords	がん / 代謝 / 低分子量GTP結合蛋白質 / Ral / Ｒａｌ / 低分子量GTP結合タンパク質 / 分子病態学 / シグナル伝達
Outline of Final Research Achievements	An inhibitor os small GTPase Ral has been developed and shown to inhibit cancer growth (Nature, 2014). Thus, the control of Ral activity is strongly noted as a drug target. We have first identified the inhibitory regulator of Ral activity, RalGAP (JBC, 2009) and reported the important role in the progression of bladder cancer (Oncogene, 2013). In the research, we have reported that the low expression of RalGAP was associated with prostate cancer progression (Carcinogenesis, in press, 2019). Further, we have found the association between RalGAP low expression and oral squamous cell carcinoma progression and also epigenetic change of RalGAP gene (in revision).
Academic Significance and Societal Importance of the Research Achievements	Ral阻害薬が抗がん剤としてのポテンシャルが示された。我々の研究成果は、前立腺癌や口腔内癌でもRalの活性化が、腫瘍悪性化に関与していることを示すものであり、Ral阻害薬開発の有用性をサポートする基礎データとなる。一方、Ralの活性化は血糖降下に寄与するという知見を得つつあり、Ralの活性制御については、代謝の面からの解析も必要と考えられる。Ralに関する基礎データを提供し、創薬等に貢献していきたいと考えている。