The mechanism of cellular tumorigenesis by a novel mTOR signaling pathway

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07255
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Sato Tatsuhiro 愛知県がんセンター(研究所), 分子腫瘍学分野, 主任研究員 (70547893)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: Rheb / SmgGDS / mTOR / mTORC1

Outline of Final Research Achievements

The mechanism of mTORC1 regulation by SmgGDS was revealed. Further, the phosphorylation sites of two proteins that are directly phosphorylated by mTORC1 were identified.
Analysis of malignant mesothelioma identified changes in the expression of genes involved in the regulation of mTORC1 activity, which were associated with the prognosis of mesothelioma patients. We found that suppression of SmgGDS expression inhibits mTORC1 activity in malignant mesothelioma cells and inhibits tumor growth in vitro and in vivo.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究はmTORC1調節機構の一端を明らかにしている。mTORC1は細胞増殖やオートファジーの制御を通じて生体の多くの機能に関与しており、本研究成果はそれらの分子機序の解明につながると期待できる。また、mTORC1制御機構の破綻はがんをはじめ、種々の疾患と密接に関連しており、これら疾患の分子機序の解明や、悪性中皮腫をはじめとする種々のがんに対する新たな治療戦略の構築が期待される。