Analysis of nuclear signaling complexes of novel Ras family and their activities to induce cellular transformation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Jichi Medical University
• Principal Investigator: Tago Kenji 自治医科大学, 医学部, 講師 (20306111)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Ras / がん / 低分子量Gタンパク質 / TRB3

Outline of Final Research Achievements

In this research project, we attempted to clarify the role of small GTPase NKiRas in the oncogenic signals. In the previous study, we concluded that NKiRas possesses the essential roles in Ras (G12V)-induced carcinogenic signals. Recently, we found that NKiRas is required for the expression of Slc14A1, a target gene of Ras-induced oncogenic signals. Interestingly, the expression of Slc14A1 was drastically suppressed by the enforced expression of TRB3, which we identified as a interacting protein of NKiRas. Taken together, it is suggested that TRB3 exhibits its tumor-suppressor activity mediated by suppressing NKi-Ras. In future project, we need to clarify the role of Slc14A1 in oncogenic signals.

Free Research Field

細胞内シグナル伝達系

Academic Significance and Societal Importance of the Research Achievements

Ras遺伝子の点変異を含むRasシグナルの異常活性化は、多くの悪性新生物（がん）の原因となることが知られており、特に難治性がんの一つである膵癌では約90%の患者でRas遺伝子の変異が見つかっている。Rasの下流シグナルに関してもMAPキナーゼをはじめとして多くの知見が集積している一方で、MAPキナーゼ経路を構成するRafキナーゼやMEKキナーゼを標的とした抗がん剤治療には、耐性を示す患者も多く存在している。本研究がNKiRasの機能を明らかにすることは、今後の新規の抗がん剤開発研究において重要な基盤となると期待される。