SOS1 regulates HCC cell epithelial-mesenchymal transition via the PI3K/AKT/mTOR pathway

Abstract

The influence of son of sevenless homolog 1 (SOS1) on invasion and metastasis of hepatocellular carcinoma (HCC) cells was investigated. HCC cells were transfected with siRNA and lentivirus to achieve SOS1 knock down/overexpression and changes in RNA and protein levels analyzed by q-PCR and Western blotting (WB). Transwell assay was utilized to assess variations in cell invasion and migration in vitro and by a lung metastasis model of liver cancer in vivo. High expression of SOS1 was observed in most human liver cancers, which indicated a worse prognosis. SOS1 knockout in HepG2 cells significantly decreased cell invasion and migration. SOS1 knockout also reduced the number of metastatic foci in a lung metastasis model of HCC established in nude mice. SOS1 knockout inhibited the epithelial-mesenchymal transition (EMT) in HepG2 cells as well as the PI3K/AKT/mTOR pathway. Overexpression of SOS1 in Huh7 cells had the opposite effect. To conclude, SOS1 may induce the EMT by the activation of the PI3K/AKT/mTOR pathway, thereby enhancing invasion, migration and metastasis of HCC cells. These findings may expose SOS1 as a new HCC therapeutic target.