ASIC1a promotes acidic microenvironment-induced HCC cells migration and invasion by inducing autophagy

Abstract

Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer with high incidence and metastatic rate. Recent studies have shown that the high metastasis of HCC is closely related to the acidic microenvironment of HCC cells. Acid-sensing ion Channel 1a (ASIC1a) plays an important role in HCC development, which can mediate tumor cell migration and invasion. However, the underlying mechanism of how ASIC1a promotes HCC cell migration and invasion in acidic microenvironments remains unclear, while autophagy may act as a mechanism for tumor cells to adapt to acidic microenvironment. Therefore, this study aims to investigate whether ASIC1a mediates autophagy and its effects on the migration and invasion of HCC cells. Interestingly, our study has shown that ASIC1a and autophagy were increased in HepG2 cells in acidic microenvironment, and both of them can promote HCC cells migration and invasion. Moreover, inhibition of ASIC1a with PcTx1 or ASIC1a ShRNA reduced the autophagy flux. Collectively, ASIC1a can promote acidic microenvironment-induced HepG2 cells migration and invasion by inducing autophagy, which may be correlated with Ca2+ influx.