Abstract: Background and purpose: It has been reported that mammalian Ste20-like kinase 4 (MST4) promotes the invasion and metastasis of tumors. In the previous research, we found that MST4 promoted invasion and metastasis of liver cancer through epithelial-mesenchymal transition. In this study, we explored the effect of MST4 on promoting the invasion and metastasis of hepatocellular carcinoma (HCC) cells by activating MAPK-ERK signaling pathway and inflammatory factors. Methods: We used real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) to detect the transcription of IL-1β, IL-6, TNF-α and CCL2 in different HCC cell lines expressing MST4 differently. Then we studied the different secretion of IL-1β, IL-6, TNF-α and CCL2 in cells using Western blot and enzyme-linked immunosorbent assay (ELISA). Results: The RNA transcription and protein translation levels of IL-1β, IL-6, TNF-α and CCL2 were significantly higher in HCC cell line with high expression of MST4 than those in the HCC cell line with lower expression of MST4 (P<0.05). We found that MST4 could change the level of phosphorylation of ERK to promote secretion of inflammatory cytokines. Conclusion: High expression of MST4 can upregulate the secretion of inflammatory factors (IL-1β, IL-6, TNF-α and CCL2) in HCC cells and enhance the ability of invasion and metastasis of HCC cells, through activating the MAPK-ERK signaling pathway.

Key words: Mammalian Ste20-like kinase 4, Hepatocellular carcinoma, Inflammatory factors, Invasion and metastasis