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.
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| http://dx.doi.org/10.1016/j.canlet.2019.07.021 | DOI Listing |
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