Caspase-3 promotes genetic instability and carcinogenesis.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Liu, X; He, Y; Li, F; Huang, Q; Kato, TA; Hall, RP; Li, C-Y

Published Date

  • April 9, 2015

Published In

Volume / Issue

  • 58 / 2

Start / End Page

  • 284 - 296

PubMed ID

  • 25866249

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2015.03.003

Language

  • eng