SOX13 regulates cancer stem-like properties and tumorigenicity in hepatocellular carcinoma cells.

Sex-determining region Y (SRY)-related high mobility group (HMG) box (SOX) proteins are pivotal transcriptional factors that play essential roles in embryonic development, cell fate decisions and cancer development. The molecular mechanism of SOX13, a member of the SOX family, in hepatocellular carcinoma (HCC) remains largely unknown. In the current study, we found that HCC cells were able to form spheroids in serum-free suspension culture and that SOX13 expression was upregulated in spheroids enriched for cancer stem cells (CSCs). Inhibition of SOX13 in HCC-LM3 and MHCC-97H cells decreased the expression of stemness-related genes; attenuated spheroid formation, anchor-dependent and anchor-independent cell proliferation and tumorigenicity; and enhanced sensitivity to drug treatment. Furthermore, based on analysis of TCGA dataset, the results indicated that SOX13 expression was obviously upregulated and closely associated with poor prognosis in HCC patients. Moreover, SOX13 was correlated with TAZ and CD24 expression. These data strongly demonstrated that SOX13 is involved in maintaining cancer stem-like properties in HCC cells and plays a critical role in HCC development.