Caspase-3 knockout attenuates radiation-induced tumor repopulation via impairing the ATM/p53/Cox-2/PGE₂ pathway in non-small cell lung cancer.

ABSTRACT: Radiotherapy is an effective treatment for non-small cell lung cancer (NSCLC). However, irradiated, dying tumor cells generate potent growth stimulatory signals during radiotherapy that promote the repopulation of adjacent surviving tumor cells to cause tumor recurrence. We investigated the function of caspase-3 in NSCLC repopulation after radiotherapy. We found that radiotherapy induced a DNA damage response (DDR), activated caspase-3, and promoted tumor repopulation in NSCLC cells. Unexpectedly, caspase-3 knockout attenuated the ataxia-telangiectasia mutated (ATM)/p53-initiated DDR by decreasing nuclear migration of endonuclease G (EndoG), thereby reducing the growth-promoting effect of irradiated, dying tumor cells. We also identified p53 as a regulator of the Cox-2/PGE₂ axis

SUBMITTER: Zhao M 

PROVIDER: S-EPMC7695367 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature