Loss of TSC1/TSC2 complex promotes cell migration through up-regulation of AKT2

【摘要】：正Tuberous sclerosis complex.(TSC) is an autosomal dominant tumor disorder caused by inactive mutations of either TSC1 or TSC2 tumor suppressor.TSC1 and TSC2 form a protein complex in restraining the activity of mTOR and loss of this protein complex leads to hyperactive mTOR,resulting in uncontrolled cell growth and tumorigenesis.We found that AKT2 was significantly increased in TSC2~(-/-) mouse embryonic fibroblasts(MEFs),compared to TSC2~(+/+) MEFs.In addition,kidney tumor tissues from Tsc2 heterozygous knockout mice also exhibited enhanced AKT2 expression.Furthermore,the elevated AKT2 expression was reversed by rapamycin,a mTOR inhibitor.Moreover,shRNA-mediated down-regulation of AKT2 expression in Tsc2~(-/-) MEFs led to markedly reduced cell migration,as measured by wound healing and transwell migration assays.We conclude that TSCl/TSC2-mTOR pathway regulates cell migration through AKT2 and suggest that AKT2 may be a potential target for the treatment of TSC.