TMEFF2 deregulation contributes to gastric carcinogenesis and indicates poor survival outcome.
发表时间：2014-12-18 11:42
Abstract
Purpose: The role and clinical implication of the transmembrane protein with EGF and two follistatin motifs 2 (TMEFF2) in gastric cancer is poorly understood. Experimental Design: Gene expression profile analyses were performed and Gene Set Enrichment Analysis(GSEA)wasusedtoexploreitsgenesignatures.AGSandMKN45cellsweretransfectedwithTMEFF2 or control plasmids and analyzed for gene expression patterns, proliferation, and apoptosis. TMEFF2 expression was knocked down with shRNAs, and theeffects on genome stability were assessed. Interactions between TMEFF2 and SHP-1 were determined by mass spectrometry and immunoprecipitation assays. Results:IntegratedanalysisrevealedthatTMEFF2expressionwassignificantlydecreasedingastriccancer casesanditsexpressionwasnegativelycorrelatedwiththepoorpathologicstage,largetumorsize,andpoor prognosis. GSEA in The Cancer Genome Atlas (TCGA) and Jilin datasets revealed that cell proliferation, apoptosis, and DNA damage–related genes were enriched in TMEFF2 lower expression patients. Gain of TMEFF2 function decreased cell proliferation by increasing of apoptosis and blocking of cell cycle in gastric cancer cells. The protein tyrosine phosphatase SHP-1 was identified as a binding partner of TMEEF2 and mediator of TMEFF2 function. TMEFF2 expression positively correlated with SHP-1, and a favorable prognosis was more likely in patients with gastric cancer with higher levels of both TMEFF2 and SHP-1. Conclusion: TMEFF2 acts as a tumor suppressor in gastric cancer through direct interaction with SHP-1 and can be a potential biomarker of carcinogenesis.
第一署名医院：仁济医院
