The Role of SIRT1 in Breast Cancer Stem Cells

Abstract

The role of SIRT1 in breast cancer stem cell has been studied in breast cancer cell lines, human breast cancer samples, and xenograft mouse model. In breast cancer cell lines, SIRT1 inhibitors cambinol and Ex527 significantly decreased CD44 expression in MDA-MB-231, CD24 expression in MDA-MB-468, and ALDH1a positive cells in MDA-MB-231. SIRT1 inhibitors significantly blocked the cell invasion in vitro, and also inhibited cancer cell migration. SIRT1 inhibitors blocked Wnt pathway showing significantly downregulation of cyclin D1 and c-Myc. SIRT1 inhibitors significantly blocked TGFbeta1 induced EMT in cancer cells. Immunohistochemitry performed on human breast cancers (N=32) showed significant high SIRT1 expression in grade 3 cancers, positive correlation between SIRT1 and vimentin, and grade 3 cancers with high stem cell expression (ALDH1a/CD44). SIRT1 expression was significantly associated with DVL3 protein. In xenograft mouse model, intramammary fat pad tumor cell inoculation generated a very good model for studying nodal metastasis for breast cancer. SIRT1 inhibitor cam. The role of SIRT1 in breast cancer stem cell has been studied in breast cancer cell lines, human breast cancer samples, and xenograft mouse model. In breast cancer cell lines, SIRT1 inhibitors cambinol and Ex527 significantly decreased CD44 expression in MDA-MB-231, CD24 expression in MDA-MB-468, and ALDH1a positive cells in MDA-MB-231. SIRT1 inhibitors significantly blocked the cell invasion in vitro, and also inhibited cancer cell migration. SIRT1 inhibitors blocked Wnt pathway showing significantly downregulation of cyclin D1 and c-Myc. SIRT1 inhibitors significantly blocked TGbinol significantly inhibited tumor growth and blocked tumor metastasis.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2015
Accession Number
AD1000553

Entities

People

  • Baoxiang Guan
  • Robert M. Brown
  • Songlin Zhang

Organizations

  • University of Texas Health Science Center at Houston

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Movement
  • Cell Physiological Processes
  • Cells
  • Colon Cancer
  • Gene Expression
  • Inhibitors
  • Inoculation
  • Lymph Nodes
  • Metastasis
  • Migration
  • Neoplasms
  • Oncology
  • Stem Cells
  • Xenografts

Fields of Study

  • Biology
  • Chemistry
  • Medicine

Readers

  • Molecular Biology and Genetics
  • Mycotoxin ecology in Amazonian ecosystems.
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology