Caspase-8 as a therapeutic target in cancer.
Caspase-8 is an apical caspase which initiates programmed cell death following death receptor ligation. This central role in apoptosis has prompted significant clinical interest in regulating caspase-8 expression and proteolytic activity. However, caspase-8 has also been found to play a number of non-apoptotic roles in cells, such as promoting activation NF-κB signaling, regulating autophagy and altering endosomal trafficking, and enhancing cellular adhesion and migration. Therefore, depending upon the specific cellular context, caspase-8 may either potentiate or suppress tumor malignancy. Accordingly, a marked heterogeneity exists in the expression patterns of caspase-8 among different tumor types. Therapeutics have been developed which can increase caspase-8 expression, yet it remains unclear whether this approach will be beneficial in all cases. Care is warranted, and the role of caspase-8 should be addressed on a case by case basis.
Stupack
Dwayne G
DG
Department of Pathology & the Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive MC0803, La Jolla, CA 92093-0803, USA. dstupack@ucsd.edu
D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D011992:Endosomes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*
D016328:NF-kappa B; C505530:CASP8 protein, human; D053181:Caspase 8
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