The myelin protein PMP2 is regulated by SOX10 and drives melanoma cell invasion

Pigment Cell Melanoma Res. 2019 May;32(3):424-434. doi: 10.1111/pcmr.12760. Epub 2018 Dec 21.

Abstract

The transcription factor sex determining region Y-box 10 (SOX10) plays a key role in the development of melanocytes and glial cells from neural crest precursors. SOX10 is involved in melanoma initiation, proliferation, invasion, and survival. However, specific mediators which impart its oncogenic properties remain widely unknown. To identify target genes of SOX10, we performed RNA sequencing after ectopic expression of SOX10 in human melanoma cells. Among nine differentially regulated genes, peripheral myelin protein 2 (PMP2) was consistently upregulated in several cell lines. Direct regulation of PMP2 by SOX10 was shown by chromatin immunoprecipitation, electrophoretic mobility shift, and luciferase reporter assays. Moreover, a coregulation of PMP2 by SOX10 and early growth response 2 in melanoma cells was found. Phenotypical investigation demonstrated that PMP2 expression can increase melanoma cell invasion. As PMP2 protein was detected only in a subset of melanoma cell lines, it might contribute to melanoma heterogeneity.

Keywords: PMP2; SOX10; Schwann cell; glial cell; heterogeneity; invasion; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Myelin P2 Protein / genetics*
  • Myelin P2 Protein / metabolism
  • Neoplasm Invasiveness
  • Promoter Regions, Genetic
  • SOXE Transcription Factors / genetics
  • SOXE Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • Myelin P2 Protein
  • PMP2 protein, human
  • SOX10 protein, human
  • SOXE Transcription Factors