Zyxin promotes hepatocellular carcinoma progression via activation the AKT/mTOR signaling pathway

Abstract To investigate the regulatory effect and specific mechanism of the actin-interacting protein zyxin (ZYX) in hepatocellular carcinoma (HCC). HCC is one of the most common malignant tumors in the world which occurrence and development areregulated by multiple genes. We found that the expression of ZYX in HCC tissues was significantly higher than that in normal liver tissues. The results of cell proliferation assay, scratch test and transwell assay showed that high expression of ZYX promoted the proliferation, migration and invasion of hepatoma cell lines (PLC/PRF/5, HCCLM3), inhibiting the expression of ZYX reduced the proliferation, migration, and invasion of hepatoma cells(SK HEP-1, Huh-7). Further analysis found that the expression of cell cycle-related proteins, cell migration and invasion-related proteins were changed when the expression of ZYX changed. Xenograft models showed similar results. The AKT/mTOR signaling pathway is a classic pathway ofcancer development. We found that the phosphorylation level of AKT/mTOR protein was up-regulated with increasing ZYX expression and down-regulated with decreasing ZYX expression. While the addition of the AKT inhibitor MK2206 counteracted the proliferation, migration and invasion of HCC cells with increasing ZYX expression, the AKT activator SC79 also restored the proliferation, migration and invasion of HCC cells with decreasing ZYX expression. Therefore, we speculate that the expression of ZYX may promoting the progression of HCC by activating AKT/mTOR signaling pathway, thereby. This is also the first time to find the mechanism of ZYX in HCC, indicating that ZYX is a possible new target for HCC treatment.