Dysadherin can enhance tumorigenesis by conferring properties of stem-like cells to hepatocellular carcinoma cells

Abstract

Background & Aims: Hepatocellular carcinoma (HCC) is associated with a high potential for metastasis and disease recurrence, even after surgical resection. The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for chemo-resistance, recurrence, and metastasis. Dysadherin is a prognostic indicator of metastasis and poor survival in many different cancer types. In this study, we investigated the possible link between dysadherin and CSC in HCC. Methods: We analyzed the functional implications of dysadherin on cancer sternness by modification of the dysadherin gene in HCC cell lines. Results: The transfection of dysadherin cDNA into the liver cancer cell line PLC/PRF/5 enhanced the properties of CSCs, including anti-apoptosis, their sphere-forming ability, side population phenotype, and tumor initiation ability in vivo. Furthermore, knockdown of dysadherin in the liver cancer cell line SK-Hep1 suppressed its stem cell-like properties. Conclusions: These results show that dysadherin give rise to properties of CSC in HCC. Therefore, these findings suggest that dysadherin may be a potential molecular prognostic marker of HCC and may aid in the development of more effective therapies.