Targeting c-FLIP in cancer.
Cellular-FLICE inhibitory protein (c-FLIP) is a key anti-apoptotic regulator that inhibits cell death mediated by the death receptors Fas, DR4, DR5, and TNF-R1. Three splice variants of c-FLIP function at the DISC level by blocking the processing and activation of procaspase-8 and -10. Overexpression of c-FLIP has been identified in many different tumour types, and its downregulation in vitro has been shown to restore apoptosis mediated by CD95L and TRAIL. c-FLIP therefore represents a promising target for cancer therapy. This review focuses on the molecular mechanisms that control c-FLIP expression and current research into inhibitors of the protein. Increasing evidence supports the investigation of c-FLIP as a therapeutic target to restore an apoptotic response in cancer cells.
INSERM, U866, Dijon F-21079, France.
Sarah
S
Shirley
Olivier
O
Micheau
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D014158:Transcription, Genetic
D000970:Antineoplastic Agents; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand