title: Role of the pro-survival molecule Bfl-1 in melanoma.
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.
authors.affiliation: Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: C K
authors.initials: CK
authors.lastname: Hind
authors.affiliation: Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Carter
authors.affiliation: Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Harris
authors.affiliation: Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: H T C
authors.initials: HT
authors.lastname: Chan
authors.affiliation: Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: S
authors.initials: S
authors.lastname: James
authors.affiliation: Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK. Electronic address: msc@soton.ac.uk.
authors.forename: M S
authors.initials: MS
authors.lastname: Cragg
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D002478:Cells, Cultured; D019610:Cytoprotection; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015778:Minor Histocompatibility Antigens; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: C096816:BCL2-related protein A1; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D046988:Proteasome Endopeptidase Complex
keywords: Apoptosis; BCL2A1; Bfl-1; Melanocytes; Melanoma