Developmental pathways activated in melanocytes and melanoma

Arch Biochem Biophys. 2014 Dec 1:563:13-21. doi: 10.1016/j.abb.2014.07.023. Epub 2014 Aug 8.

Abstract

Cutaneous malignant melanomas originate primarily within epidermal melanocytic cells. Melanoma cells share many characteristics with melanocyte precursors, suggesting that melanoma cells utilize the developmental programs of their normal counterpart for their own progression. The pigmentation system provides an advantageous model to assess survival pathway interactions in the melanocytic lineage, as genetic alterations controlling melanocyte development can be easily detectable by coat color phenotype that do not affect the viability of an animal. By integrating combinatorial gene knockout approaches, cell-based assays and immunohistochemical observations, recent studies have illustrated several genes and pathways that play important roles both in melanocyte specification and maintenance and in melanoma formation and progression. We are reviewing those genes and pathways to understand the connection between normal and cancerous development and to reveal therapeutic potential of targeting developmental pathways for melanoma therapy.

Keywords: Beta-catenin; Endothelin; MITF; Melanocytes; Melanoma; Notch; Signaling pathways; Sox10; Sox9; Wnt.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Disease Progression
  • Endothelins / metabolism
  • Humans
  • Melanocytes / metabolism*
  • Melanocytes / pathology
  • Melanoma / etiology
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Phenotype
  • Receptors, Notch / metabolism
  • SOX Transcription Factors / metabolism
  • Signal Transduction
  • Skin Neoplasms / etiology
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Wnt Signaling Pathway
  • beta Catenin / metabolism

Substances

  • Endothelins
  • Microphthalmia-Associated Transcription Factor
  • Receptors, Notch
  • SOX Transcription Factors
  • beta Catenin