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

• Bfl-1 is highly expressed in melanoma cells and regulated by NFκB and the proteasome.
• Knock down of Bfl-1 levels increased cytotoxicity to relevant treatment agents, while overexpression decreased it.
• Primary melanocytes exhibit source-dependent expression levels of Bfl-1.

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.