Dysadherin Influences Cancer Stemness and Aggressiveness in Hepatocellular Carcinoma via FAK/YAP Axis

Abstract

Cancer stem-like cells (CSCs) are believed to play a critical role in the development, progression, and therapeutic resistance of hepatocellular carcinoma (HCC). Dysadherin is cell membrane glycoprotein that is linked to cancer progression by endowing HCC with CSC properties. However, its underlying mechanisms is not fully understood. Here, comprehensive bioinformatics analysis suggested that HCC patients expressing dysadherin at high levels were correlated with activation of the Yes-associated protein 1 (YAP) signaling pathway. Correspondingly, dysadherin deficiency reduced cancer stemness and aggressiveness in a mouse model of HCC by suppressing YAP signaling. Furthermore, several gain and loss of function study have proven that dysadherin triggers the FAK/YAP/OCT4 axis in HCC cells to activate the CSC characteristics. In conclusion, we elucidate the novel mechanism that dysadherin promotes function of cancer stemness by FAK-YAP axis, which may represent a potential therapeutic strategy by suppressing cancer aggressiveness.