SH3GL1 Promotes Liver Tumorigenesis by Activating β-Catenin Signaling

Abstract Hepatocellular carcinoma (HCC) is the most prevalent subtype of primary liver cancer and one of the leading causes of cancer-related death in the world. Liver cancer stem cells (CSCs) have been well established to be responsible for liver tumorigenesis, metastasis, drug resistance and tumor relapse. Yet the underlying mechanisms of CSCs self-renewal and maintenance are poorly understood. Here, we first report that SH3GL1 was dramatically upregulated in liver cancer and higher SH3GL1 expression was significantly correlates with worse clinical outcomes of liver cancer patients. Loss of function experiments demonstrate that SH3GL1 functions as a novel oncogene to potentiate liver cancer cell proliferation and liver CSCs self-renewal maintenance in vitro as well as xenograft tumor grow in vivo. Mechanistically, our study reveals that SH3GL1 facilitates liver CSCs by physically interacting with and activating β-catenin signaling. Our study characterizes SH3GL1 as a new regulator of oncogenic β-catenin signaling and defines newly therapeutic target for liver cancer patients.