University of Texas Health Science Center Houston United States
Cancer stem cells CSCs can initiate and sustain tumor growth and escape chemoradiation therapies, result in cancer relapse and poor prognoses. Epithelial Mesenchymal transition EMT occurred in CSCs are responsible for cancer invasion and metastasis. SIRT1, a class III histone deacetylase was previously described to promote breast cancer stem cells BCSCs, however, the association between SIRT1 and breast cancer is uncertain. In this study, we detected SIRT1 possessed high expressions in higher grade of breast cancer patients which harbor CSC properties, and SIRT1 expression is associated with cancer stem cells in breast cancer specimen by ALDH1aCD44 double staining. SIRT1 inhibitors significantly reduced breast cancer stem cell population by flow cytometry study using CD24CD44 and ALDH1a. SIRT1 inhibition greatly down-regulate the genes of cancer stem cells such as Nanog and SOX2, and genes of EMT markers such as vimentin. In xenograft study, SIRT1 inhibitor cambinol significantly inhibited tumor growth and completely blocked tumor cell metastasis comparing with the control mice. SIRT1 inhibitors also inhibit the drug resistance to cisplatin of tumor cells. Our results showed SIRT1 regulate cancer stem cells through Wnt-catenin pathway and DVL-3 appears to be important regulate factor. Our results suggest that SIRT1 potentially acts as a prognostic factor in breast cancer and plays an important role to promote BCSCs. Inhibition of SIRT1 may have significant therapeutic value in breast cancer.