Delayed caspase‐8 activation and enhanced integrin β1‐activated FAK underpins anoikis in oesophageal carcinoma cells harbouring mt p53‐R175H

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 resis...

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Published in:Cell biology international 2011-08, Vol.35 (8), p.819-826
Main Authors: Fanucchi, Stephanie, Veale, Robin B
Format: Article
Language:English
Subjects:
Anoikis
Apoptosis
Caspase 8 - metabolism
Cell Adhesion - genetics
Cell Line, Tumor
Enzyme Activation
Esophageal Neoplasms - metabolism
Extracellular Matrix - metabolism
FAK
Fas
Fluorescent Antibody Technique, Indirect
Focal Adhesion Kinase 1 - metabolism
Humans
Immunoblotting
Immunoprecipitation
Integrin beta1 - metabolism
mt p53‐R175H
Mutation
oesophageal carcinoma
Phosphorylation
Signal Transduction - genetics
staurosporine
Tumor Suppressor Protein p53 - genetics
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Summary: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.
ISSN:1065-6995
1095-8355
DOI:10.1042/CBI20100894