Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells

Autor: Yi Jang Lee, Chih Wen Peng, Yao Huei Huang, Qiu Yu Chuah, Shu Jun Chiu, Yi Fen Hsieh, Pei Ming Yang
Rok vydání: 2014
Předmět:
Zdroj: Autophagy. 10:1212-1228
ISSN: 1554-8635
1554-8627
DOI: 10.4161/auto.28772
Popis: Ionizing radiation induces cellular senescence to suppress cancer cell proliferation. However, it also induces deleterious bystander effects in the unirradiated neighboring cells through the release of senescence-associated secretory phenotypes (SASPs) that promote tumor progression. Although autophagy has been reported to promote senescence, its role is still unclear. We previously showed that radiation induces senescence in PTTG1-depleted cancer cells. In this study, we found that autophagy was required for the radiation-induced senescence in PTTG1-depleted breast cancer cells. Inhibition of autophagy caused the cells to switch from radiation-induced senescence to apoptosis. Senescent cancer cells exerted bystander effects by promoting the invasion and migration of unirradiated cells through the release of CSF2 and the subsequently activation of the JAK2-STAT3 and AKT pathways. However, the radiation-induced bystander effects were correlated with the inhibition of endogenous autophagy in bystander cells, which also resulted from the activation of the CSF2-JAK2 pathway. The induction of autophagy by rapamycin reduced the radiation-induced bystander effects. This study reveals, for the first time, the dual role of autophagy in radiation-induced senescence and bystander effects.
Databáze: OpenAIRE