title: Delayed caspase-8 activation and enhanced integrin β1-activated FAK underpins anoikis in oesophageal carcinoma cells harbouring mt p53-R175H.
abstract: FAK (focal adhesion kinase)-mediated signalling reportedly suppresses caspase-8 activation and, as a consequence, rescues epithelial cells from Fas-mediated anoikis. Critical was the use of a HOSCC (human oesophageal squamous carcinoma) cell line harbouring mt (mutant) p53-R175H and displaying resistance to detachment and Tyr397 dephosphorylation of FAK. Here we show, although caspase-8 activation is delayed in the mt p53-R175H cell line, comparable apoptotic events evidenced in the wt (wild type) p53 HOSCC cell lines could be induced in the mt p53-R175H cell line by strengthening the apoptotic stimulus. Significant to anoikis-related regulation, the delay in caspase-8 activation was accompanied by the maintenance of FAK Tyr397 phosphorylation, integrin β1-associated FAK and a FAK/caspase-8 complex. Thus, mt p53-R175H may desensitize tumours to Fas-mediated anchorage-independent death via a FAK-dependent mechanism.
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2050, South Africa.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fanucchi
authors.forename: Robin B
authors.initials: RB
authors.lastname: Veale
mesh_terms: D023102:Anoikis; D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D019012:Integrin beta1 / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D019012:Integrin beta1; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C505530:CASP8 protein, human; D053181:Caspase 8