Non-apoptotic Roles of Caspases in Stem Cell Biology, Carcinogenesis, and Radiotherapy

Abstract

To summarize recent findings on novel roles of caspases in stem cell biology, tumor repopulation, and tissue regeneration. Contrary to the long-held notion that apoptotic caspases are exclusively executioners of programmed cell death, an abundance of evidence is emerging that activation of caspases does not inevitably lead to cell death. It is now known that sublethal activation of caspases occurs in development, stem cell differentiation, epigenetic reprogramming, and a whole host of other key biological processes. Important for cancer biology, recent studies show that activation of caspases in tumors facilitates carcinogenesis, metastasis, and tumor relapse after cancer treatment. We have found that apoptotic cells secrete prostaglandins to stimulate proliferation of neighboring cells. This pathway functions to regenerate tissues and stem cells in multiple organisms, but it also poses problems in emerging tumor resistance to chemotherapy and radiotherapy. Novel findings on caspases are contrary to established paradigms and might explain why cancer therapies aimed at activating apoptotic caspases have not been very successful in the clinic. In this brief review, we summarize some novel findings regarding caspases with the hope of stimulating more interest in this nascent but increasingly important research area. Better understanding of the diverse roles of caspases may one day help us establish novel approaches for treating cancer.