title: Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells.
abstract: 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.
authors.affiliation: Department of Life Sciences; Tzu Chi University; Hualien, Taiwan.
authors.forename: Yao-Huei
authors.initials: YH
authors.lastname: Huang
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery; College of Medical Science and Technology; Taipei Medical University; Taipei, Taiwan.
authors.forename: Pei-Ming
authors.initials: PM
authors.lastname: Yang
authors.affiliation: Department of Life Sciences; Tzu Chi University; Hualien, Taiwan.
authors.forename: Qiu-Yu
authors.initials: QY
authors.lastname: Chuah
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences; National Yang-Ming University; Taipei, Taiwan.
authors.forename: Yi-Jang
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Life Sciences; Tzu Chi University; Hualien, Taiwan.
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Hsieh
authors.affiliation: Department of Life Sciences; Tzu Chi University; Hualien, Taiwan.
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Peng
authors.affiliation: Department of Life Sciences; Tzu Chi University; Hualien, Taiwan; Institute of Radiological Sciences; Tzu Chi Technology College; Hualien, Taiwan.
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Chiu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D024201:Bystander Effect / Q000187:drug effects / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D016922:Cellular Senescence / Q000187:drug effects / Q000528:radiation effects*; D002645:Chickens; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011839:Radiation, Ionizing; D050796:STAT3 Transcription Factor / Q000378:metabolism; D064249:Securin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D050796:STAT3 Transcription Factor; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt
keywords: angiogenesis; autophagy; invasion; migration; radiation; senescence-associated secretory phenotypes