CXCL17 promotes cell metastasis and inhibits autophagy via the LKB1-AMPK pathway in hepatocellular carcinoma

Abstract As an innovative CXC chemokine, CXCL17 has a mysterious clinical significance and modulating influence on hepatocellular carcinoma (HCC). Our study examined the activity and mechanisms of CXCL17 on growth, autophagy, and metastasis of HCC. Upregulation of CXCL17 expression was observed in HCC, which is correlated with poorer histological stages and outcomes. Elevation of CXCL17 expression promoted proliferation, invasion, and migration and decreased LC-3B biosynthesis and p62 protein reduction, which are known to stimulate autophagy. However, silencing of CXCL17 inhibited the development of these cancerous phenotypes. Furthermore, AMPK was stimulated after knockdown of CXCL17. This stimulation, as well as stimulation of autophagy was caused by liver kinase B1 (LKB1), whose function is induced by knockdown CXCL17. Additionally, knockdown of CXCL17 enhanced nuclear translocation of LKB1. Altogether, these findings suggest that elevated CXCL17 expression in HCC promotes malignant reactions in malignant cells. Our research offers new evidence that chemokine CXCL17 reinforces malignant invasion and suppresses autophagy via the LKB1-AMPK pathway.