| First Author | Liu X | Year | 2015 |
| Journal | Mol Cell | Volume | 58 |
| Issue | 2 | Pages | 284-96 |
| PubMed ID | 25866249 | Mgi Jnum | J:316026 |
| Mgi Id | MGI:6832245 | Doi | 10.1016/j.molcel.2015.03.003 |
| Citation | Liu X, et al. (2015) Caspase-3 promotes genetic instability and carcinogenesis. Mol Cell 58(2):284-96 |
| abstractText | Apoptosis is typically considered an anti-oncogenic process since caspase activation can promote the elimination of genetically unstable or damaged cells. We report that a central effector of apoptosis, caspase-3, facilitates rather than suppresses chemical- and radiation-induced genetic instability and carcinogenesis. We found that a significant fraction of mammalian cells treated with ionizing radiation can survive despite caspase-3 activation. Moreover, this sublethal activation of caspase-3 promoted persistent DNA damage and oncogenic transformation. In addition, chemically induced skin carcinogenesis was significantly reduced in mice genetically deficient in caspase-3. Furthermore, attenuation of EndoG activity significantly reduced radiation-induced DNA damage and oncogenic transformation, identifying EndoG as a downstream effector of caspase-3 in this pathway. Our findings suggest that rather than acting as a broad inhibitor of carcinogenesis, caspase-3 activation may contribute to genome instability and play a pivotal role in tumor formation following damage. |
