Breast cancer suppressor candidate-1 (BCSC-1) is a melanoma tumor suppressor that down regulates MITF

Pigment Cell Melanoma Res. 2012 Jul;25(4):482-7. doi: 10.1111/j.1755-148X.2012.01018.x.

Abstract

Understanding the molecular aberrations involved in the development and progression of metastatic melanoma (MM) is essential for a better diagnosis and targeted therapy. We identified breast cancer suppressor candidate-1 (BCSC-1) as a novel tumor suppressor in melanoma. BCSC-1 expression is decreased in human MM, and its ectopic expression in MM-derived cell lines blocks tumor formation in vivo and melanoma cell proliferation in vitro while increasing cell migration. We demonstrate that BCSC-1 binds to Sox10, which down regulates MITF, and results in a switch of melanoma cells from a proliferative to a migratory phenotype. In conclusion, we have identified BCSC-1 as a tumor suppressor in melanoma and as a novel regulator of the MITF pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanoma / genetics*
  • Melanoma / pathology
  • Mice
  • Microphthalmia-Associated Transcription Factor / genetics*
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism*
  • Protein Binding
  • SOXE Transcription Factors / metabolism
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Tumor Suppressor Proteins / metabolism

Substances

  • Microphthalmia-Associated Transcription Factor
  • Neoplasm Proteins
  • SOX10 protein, human
  • SOXE Transcription Factors
  • Tumor Suppressor Proteins
  • VWA5A protein, human