Blockade of Wnt/β-catenin Signaling Suppresses Breast Cancer Metastasis by Inhibiting CSC-like Phenotype

Sci Rep. 2015 Jul 23;5:12465. doi: 10.1038/srep12465.

Abstract

The identification of cancer stem cells (CSCs) represents an important milestone in the understanding of chemodrug resistance and cancer recurrence. More specifically, some studies have suggested that potential metastasis-initiating cells (MICs) might be present within small CSC populations. The targeting and eradication of these cells represents a potential strategy for significantly improving clinical outcomes. A number of studies have suggested that dysregulation of Wnt/β-catenin signaling occurs in human breast cancer. Consistent with these findings, our previous data have shown that the relative level of Wnt/β-catenin signaling activity in breast cancer stem cells (BCSCs) is significantly higher than that in bulk cancer cells. These results suggest that BCSCs could be sensitive to therapeutic approaches targeting Wnt/β-catenin signaling pathway. In this context, abnormal Wnt/β-catenin signaling activity may be an important clinical feature of breast cancer and a predictor of poor survival. We therefore hypothesized that Wnt/β-catenin signaling might regulate self-renewal and CSC migration, thereby enabling metastasis and systemic tumor dissemination in breast cancer. Here, we investigated the effects of inhibiting Wnt/β-catenin signaling on cancer cell migratory potential by examining the expression of CSC-related genes, and we examined how this pathway links metastatic potential with tumor formation in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / secondary*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Female
  • Glycoproteins / administration & dosage
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Inbred BALB C
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*
  • Sulfonamides / administration & dosage
  • Treatment Outcome
  • Wnt Signaling Pathway / drug effects*

Substances

  • FH535
  • Glycoproteins
  • Intracellular Signaling Peptides and Proteins
  • Sulfonamides
  • WD repeat containing planar cell polarity effector