Dichloroacetate attenuates the stemness of hepatocellular carcinoma cells via promoting nucleus-cytoplasm translocation of YAP

The antitumor effects of dichloroacetate (DCA) have been widely explored, however, its roles in hepatocellular carcinoma (HCC) progression are still unclear. In the current work, we found that DCA had little effects on HCC cell viability, but could attenuate the stemness of HCC cells, which is evident by decreasing the tumor sphere-formation ability, ALDH activity and the expression of stemness critical regulators. Mechanistic studies based on RNA-sequencing data showed that DCA activated the Hippo pathway. Furthermore, we indicated that DCA promoted the nucleus-cytoplasm translocation of YAP, but not TAZ, another critical executor of Hippo pathway. Moreover, suppressing of Hippo pathway using XMU-MP-1, an inhibitor of Hippo pathway, partially abrogated DCA-induced inhibitory effects on HCC cell stemness. This work suggests that DCA might be a potential inhibitor for HCC progression.