2013 Fiscal Year Final Research Report

The role of mTOR signalng in colorectal cancer

Research Project

Project/Area Number	24790382
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Experimental pathology
Research Institution	愛知県がんセンター(研究所) (2013) Kyoto University (2012)
Principal Investigator	FUJISHITA Teruaki 愛知県がんセンター(研究所), 分子病態学部, 研究員 (50511870)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	腫瘍 / マウスモデル
Research Abstract	mTORC1 signaling promotes cell growth and protein synthesis, and is frequently activated in various types of cancer. However, its involvement in the formation and progression of colorectal cancer remains unclear. This study investigated the roles of mTORC1 signaling in colorectal cancer by treating cis-Apc/Smad4 compound mutant mice, a mouse model for colon adenocarcinoma, with mTOR inhibitors. Although both the mTORC1-selective inhibitor RAD001 and the mTOR kinase inhibitor AZD8055 reduced colon cancer formation and prolonged the survival of cis-Apc/Smad4 mice, they failed to suppress the local invasion of colon cancer cells. Analysis of possible feedback loops revealed EGFR activation in colorectal cancer cells treated with the mTOR inhibitors, suggesting that the resistance to the mTOR inhibitors might have been acquired through activation of EGFR. Combination treatment with EGFR inhibitors may potentiate the efficacy of the mTOR inhibitors against colorectal cancer.

(5 results)