Microphthalmia-associated transcription factor expression levels in melanoma cells contribute to cell invasion and proliferation

Exp Dermatol. 2015 Jul;24(7):481-4. doi: 10.1111/exd.12724.

Abstract

Microphthalmia-associated transcription factor (MITF) is a nodal point in melanoma transcriptional network that regulates dozens of genes with critical functions in cell differentiation, proliferation and survival. Highly variable MITF expression levels exist in tumor cell subpopulations conferring marked heterogeneity and plasticity in the tumor tissue. A model has been postulated whereby lower MITF levels favour cell invasion and suppress proliferation, whereas high levels stimulate differentiation and proliferation. Additionally, MITF is considered to be a prosurvival gene and a lineage addiction oncogene in melanoma. Herein, we review how MITF expression may affect the melanoma phenotype with consequences on the survival, invasion and metastasis of melanoma cells, and we discuss the research challenges.

Keywords: BRN2; GLI2; SOX2; melanoma; microphthalmia-associated transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Cell Survival
  • Epithelial-Mesenchymal Transition
  • Gene Expression
  • Homeodomain Proteins / metabolism
  • Humans
  • Kruppel-Like Transcription Factors / metabolism
  • MAP Kinase Signaling System
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Microphthalmia-Associated Transcription Factor / genetics
  • Microphthalmia-Associated Transcription Factor / metabolism*
  • Models, Biological
  • Neoplasm Invasiveness
  • Nuclear Proteins / metabolism
  • POU Domain Factors / metabolism
  • Protein Stability
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • SOXB1 Transcription Factors / metabolism
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology*
  • Tumor Microenvironment
  • Zinc Finger Protein Gli2

Substances

  • GLI2 protein, human
  • Homeodomain Proteins
  • Kruppel-Like Transcription Factors
  • MITF protein, human
  • MicroRNAs
  • Microphthalmia-Associated Transcription Factor
  • Nuclear Proteins
  • POU Domain Factors
  • RNA, Neoplasm
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Zinc Finger Protein Gli2
  • transcription factor Brn-2