Squamous cell carcinoma antigen 1 promotes caspase-8-mediated apoptosis in response to endoplasmic reticulum stress while inhibiting necrosis induced by lysosomal injury.

摘要: Squamous cell carcinoma antigen 1 (SCCA1) is a member of the serine protease inhibitor (serpin) family proteins, whose target proteases include cathepsins. Initially identified as serological marker for advanced squamous carcinomas cervix, SCCA1 has also been found to be associated with other cancer types epithelial or endodermal origins such lung cancer, head and neck melanoma, hepatocellular carcinoma. While biological function remains largely unclear, it believed limit cellular damage resulting from lysosomal cathepsin release. Here, we show that acts molecular switch inhibits death induced by injury DNA alkylating agents hypotonic shock, whereas promotes caspase-8-mediated apoptosis in response endoplasmic reticulum (ER) stress. In ER stress, blocks both proteasomal protein degradation pathways enhances interaction between sequestosome 1/p62 caspase-8, which leads aggregation intracellular caspase-8 its subsequent cleavage activation. Hence, on one hand, while, sensitizes cells stress activating independently receptor apoptotic pathway.