HGF/c-MET Signaling in Melanocytes and Melanoma

Int J Mol Sci. 2018 Dec 3;19(12):3844. doi: 10.3390/ijms19123844.

Abstract

Hepatocyte growth factor (HGF)/ mesenchymal-epithelial transition factor (c-MET) signaling is involved in complex cellular programs that are important for embryonic development and tissue regeneration, but its activity is also utilized by cancer cells during tumor progression. HGF and c-MET usually mediate heterotypic cell⁻cell interactions, such as epithelial⁻mesenchymal, including tumor⁻stroma interactions. In the skin, dermal fibroblasts are the main source of HGF. The presence of c-MET on keratinocytes is crucial for wound healing in the skin. HGF is not released by normal melanocytes, but as melanocytes express c-MET, they are receptive to HGF, which protects them from apoptosis and stimulates their proliferation and motility. Dissimilar to melanocytes, melanoma cells not only express c-MET, but also release HGF, thus activating c-MET in an autocrine manner. Stimulation of the HGF/c-MET pathways contributes to several processes that are crucial for melanoma development, such as proliferation, survival, motility, and invasiveness, including distant metastatic niche formation. HGF might be a factor in the innate and acquired resistance of melanoma to oncoprotein-targeted drugs. It is not entirely clear whether elevated serum HGF level is associated with low progression-free survival and overall survival after treatment with targeted therapies. This review focuses on the role of HGF/c-MET signaling in melanoma with some introductory information on its function in skin and melanocytes.

Keywords: HGF; MET; drug resistance; invasive growth; melanocytes; melanoma; skin; tumor microenvironment; wound healing.

Publication types

  • Review

MeSH terms

  • Animals
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Melanocytes / metabolism*
  • Melanoma / metabolism*
  • Models, Biological
  • Proto-Oncogene Proteins c-met / metabolism*
  • Signal Transduction*

Substances

  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met