THE ROLE OF STEM CELL FACTOR SALL4 IN HEPATOCELLULAR CARCINOMA

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Treatment of HCC remains abysmal; discovery of novel pathways implicated in hepatocarcinogenesis is needed for more effective therapeutics. SALL4 is a stem cell factor that regulates ESC self-renewal properties. It is also an emerging oncogene. The aim of this thesis is to study the potential roles of SALL4 as a molecular biomarker for HCC and its functional roles in promoting hepatocarcinogenesis. In this study, we report a novel oncofetal protein in HCC, SALL4, which allows identification of a progenitor HCC subset with worse prognosis, and offers a potential treatment target. Importantly, our multivariate analysis confirmed that SALL4 is an independent prognostic factor for HCC. Gain- and loss-of-function studies confirmed that SALL4 is critical for hepatocarcinogenesis. Importantly, we demonstrated that a peptide can block the oncogenic function of SALL4 in HCC by modulating the PTEN/AKT pathway.