The WNT/Beta-catenin pathway in melanoma

Front Biosci. 2006 Jan 1;11:733-42. doi: 10.2741/1831.

Abstract

The Wnt/beta-catenin pathway is involved in various cellular activities--including determination, proliferation, migration and differentiation--in embryonic development and adult homeostasis. The deregulation or constitutive activation of the Wnt/beta-catenin pathway may lead to cancer formation. This review focuses on the role of the Wnt/beta-catenin canonical signaling pathway in the melanocyte lineage, and more specifically, in melanoma. Several components of the Wnt/beta-catenin pathway, such as APC, ICAT, LEF1 and beta-catenin are modified in melanoma tumors and cell lines, leading to activation of this signaling. A hallmark of the activation of this pathway is the presence of beta-catenin in the nucleus. Indeed, beta-catenin is found in about 30% of human melanoma nuclei, indicating a potentially specific role for this signaling pathway in this aggressive type of cancer. Beta-catenin can induce ubiquitous genes such as myc or cyclinD1, cell lineage-restricted genes such as Brn2 and melanocyte-specific genes such as Mitf-M and Dct. The Mitf-M and Brn-2 genes encode transcription factors. Mitf plays a critical role in melanocyte survival, proliferation and differentiation. Brn-2 is involved in melanoma proliferation. Determining how the Wnt/beta-catenin signaling pathway, alone or with other pathways, orchestrates the induction of target genes involved in a diverse range of activities represents a major challenge in research into melanoma formation and tumor progression.

Publication types

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

MeSH terms

  • Cell Adhesion Molecules / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cell Membrane / metabolism
  • Cell Movement
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cyclin D1 / metabolism
  • Cytoplasm / metabolism
  • Hepatocytes / metabolism
  • Homeodomain Proteins / metabolism
  • Humans
  • Intramolecular Oxidoreductases / metabolism
  • Melanocytes / metabolism
  • Melanoma / metabolism
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Neural Crest / metabolism
  • POU Domain Factors / metabolism
  • Signal Transduction
  • Transcription, Genetic
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • Cell Adhesion Molecules
  • Homeodomain Proteins
  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • NRCAM protein, human
  • POU Domain Factors
  • Wnt Proteins
  • beta Catenin
  • transcription factor Brn-2
  • Cyclin D1
  • Intramolecular Oxidoreductases
  • dopachrome isomerase