Role of the pro-survival molecule Bfl-1 in melanoma

Int J Biochem Cell Biol. 2015 Feb:59:94-102. doi: 10.1016/j.biocel.2014.11.015. Epub 2014 Dec 6.

Abstract

Bfl-1 is a pro-survival Bcl-2 family member overexpressed in a subset of chemoresistant tumours, including melanoma. Here, we characterised the expression and regulation of Bfl-1 in normal and malignant melanocytes and determined its role in protecting these cells from chemotherapy-induced apoptosis. Bfl-1 was mitochondrially resident in both resting and apoptotic cells and experienced regulation by the proteasome and NFκB pathways. siRNA-mediated knockdown enhanced sensitivity towards various relevant drug treatments, with forced overexpression of Bfl-1 protective. These findings identify Bfl-1 as a contributor towards therapeutic resistance in melanoma cells and support the use of NFκB inhibitors alongside current treatment strategies.

Keywords: Apoptosis; BCL2A1; Bfl-1; Melanocytes; Melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Survival
  • Cells, Cultured
  • Cytoprotection
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanocytes / metabolism
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology*
  • Minor Histocompatibility Antigens
  • Mitochondria / metabolism
  • Mutation / genetics
  • NF-kappa B / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / genetics
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology*

Substances

  • BCL2-related protein A1
  • Minor Histocompatibility Antigens
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Proteasome Endopeptidase Complex