Effects of alanine-serine-cysteine transporter 2 on proliferation and invasion of hepatocellular carcinoma

Metabolic reprogramming is a major feature of tumors, and tumor cells adapt to their glutamine needs by up-regulating the alanine-serine-cysteine transporter 2(ASCT2). It was found that the ASCT2 expression in hepatocellular carcinoma (HCC) tissues was significantly higher than that in normal liver tissues. In addition, the higher expression of ASCT2 in HCC patients was closely associated with poor survival.The knockdown of ASCT2 inhibited the proliferation, clone formation, migration and invasion of HCC cells in vitro.Cell cycle analysis suggested that knockdown of ASCT2 inhibited the proportion of HCC cells in the S phase. In vivo tumorigenic assay confirmed that the knockdown of ASCT2 in HCC cells could significantly inhibit tumor growth.Further studies showed that the knockdown of ASCT2 significantly reduced mitochondrial oxidative phosphorylation(OXPHOS),ATP production,and the phosphorylation level of AKT/S6 in HCC cells.Overall, our results showed that knockdown of ASCT2 could inhibit the malignancy of HCC cells. In addition, the mitochondrial metabolism and phosphorylation level of the AKT/S6 signaling pathway of HCC cells were also inhibited following the ASCT2 inhibition, suggesting that the dysregulated mitochondrial metabolism and abnormal activation of AKT/S6 signaling pathway were closely associated with the HCC progression.