Abstract
Hepatocellular carcinoma (HCC) is a highly malignant liver tumor. The presence of cancer stem cells (CSCs) figures prominently in tumor invasion, therapeutic resistance and tumor recurrence resulting in poor outcome and limited therapeutic options. Wnt/β-catenin signaling is essential for cancer stem cell regulation and tumorigenesis in HCC, but its molecular mechanisms are not fully understood. Here, we demonstrate that β-catenin is overexpressed in liver CSCs, and its expression level is positively correlated with SIRT1 in HCC specimens. SIRT1 regulates the protein stability of β-catenin, thereby affecting the transcriptional activity of Wnt/β-catenin signaling in liver CSCs. Mechanistically, we show that nuclear accumulation of β-catenin results from deacetylation mediated by SIRT1. Further, nuclear β-catenin promotes the transcription of Nanog to help maintain self-renewal of liver CSCs. Taken together, our findings indicate that the deacetylation of β-catenin by SIRT1 represents a critical mechanism for regulating liver CSCs self-renewal and tumorigenesis. It provides an improved understanding of molecular mechanisms underlying β-catenin activation and tumorigenesis in HCC.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
