Ubiquitin ligase UBE3C promotes melanoma progression by increasing epithelial-mesenchymal transition in melanoma cells

Oncotarget. 2016 Mar 29;7(13):15738-46. doi: 10.18632/oncotarget.7393.

Abstract

Melanoma is the most aggressive type of skin cancer, exhibiting extensive local invasion and early distant metastasis. Aberrant expression of ubiquitin-protein ligase E3C (UBE3C) plays a key role in tumor development and progression. In the present study, we analyzed UBE3C expression in samples of cancerous and normal skin tissue. Levels of UBE3C expression were much higher in primary and metastatic melanoma tissues than in normal skin, cutaneous squamous cell carcinoma or basal cell carcinoma. Melanoma cells overexpressing UBE3C frequently exhibited a mesenchymal phenotype, including reduced expression of the epithelial marker E-cadherin and expression of the mesenchymal marker vimentin. Knockdown of UBE3C expression in melanoma cells significantly suppressed melanoma growth and progression. Furthermore, silencing UBE3C led to increased E-cadherin expression and decreased vimentin and Snail1 expression. Thus UBE3C promotes melanoma progression, possibly by inducing epithelial-mesenchymal transition in melanoma cells. Inhibiting UBE3C activity may suppress melanoma invasion and metastasis and may represent a targeted therapeutic approach.

Keywords: UBE3C; invasion and metastasis; melanoma; ubiquitin ligase.

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Disease Progression
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Humans
  • Male
  • Melanoma / enzymology*
  • Melanoma / pathology*
  • Middle Aged
  • Skin Neoplasms / enzymology*
  • Skin Neoplasms / pathology*
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • UBE3C protein, human
  • Ubiquitin-Protein Ligases

Supplementary concepts

  • Melanoma, Cutaneous Malignant