SOX2 promotes tumor metastasis by stimulating epithelial-to-mesenchymal transition via regulation of WNT/β-catenin signal network

Cancer Lett. 2013 Aug 19;336(2):379-89. doi: 10.1016/j.canlet.2013.03.027. Epub 2013 Mar 30.

Abstract

SOX2 was reported to promote metastasis in various tumor tissues; however the underlying mechanisms remain elusive. Here, we disclosed that SOX2 improves metastasis of breast and prostate cancer cells by promoting epithelial-to-mesenchymal transition (EMT) through WNT/β-catenin, but not TGF-β or Snail1 signaling. Dual luciferase assay and chromatin immunoprecipitation revealed activation and binding of SOX2 on promoter region of β-catenin. In addition, SOX2 affects the protein expression levels of DKK3, DVL1 and DVL3, which are regulators or downstream molecules of WNT signaling. Taken together, our findings demonstrated β-catenin as one of vital downstream molecules that mediate the EMT induced by SOX2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Animals
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Chemokines
  • Dishevelled Proteins
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • MCF-7 Cells
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Phosphoproteins / biosynthesis
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Signal Transduction
  • Wnt Proteins / metabolism*
  • Xenograft Model Antitumor Assays
  • beta Catenin / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • CTNNB1 protein, human
  • Chemokines
  • DKK3 protein, human
  • DVL1 protein, human
  • DVL3 protein, human
  • Dishevelled Proteins
  • Dvl1 protein, mouse
  • Dvl3 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Phosphoproteins
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Wnt Proteins
  • beta Catenin