Accession Number : AD1023465


Title :   The Role of SIRT1 In Breast Cancer Stem Cells


Descriptive Note : Technical Report,01 Jul 2013,30 Jun 2016


Corporate Author : University of Texas Health Science Center Houston United States


Personal Author(s) : Zhang,Songlin


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1023465.pdf


Report Date : 01 Sep 2016


Pagination or Media Count : 21


Abstract : Cancer stem cells (CSCs) can initiate and sustain tumor growth and escape chemo/radiation 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 ALDH1a/CD44 double staining. SIRT1 inhibitors significantly reduced breast cancer stem cell population by flow cytometry study using CD24/CD44 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.


Descriptors :   breast cancer , stem cells , inhibitors , MIGRATION , IMMUNOCHEMISTRY , dyes , cell line , neoplasms , chemotherapy , proteins


Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE