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

Yao Huei Huang, Pei Ming Yang, Qiu Yu Chuah, Yi Jang Lee, Yi Fen Hsieh, Chih Wen Peng, Shu Jun Chiu

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1212-1228
Number of pages17
JournalAutophagy
Volume10
Issue number7
DOIs
Publication statusPublished - 2014

Fingerprint

Bystander Effect
Autophagy
Radiation
Breast Neoplasms
Neoplasms
Cell Aging
Sirolimus
Ionizing Radiation
Cell Movement
Cell Proliferation
Apoptosis
Phenotype

Keywords

  • Angiogenesis
  • Autophagy
  • Invasion
  • Migration
  • Radiation
  • Senescence-associated secretory phenotypes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Huang, Y. H., Yang, P. M., Chuah, Q. Y., Lee, Y. J., Hsieh, Y. F., Peng, C. W., & Chiu, S. J. (2014). Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells. Autophagy, 10(7), 1212-1228. https://doi.org/10.4161/auto.28772

Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells. / Huang, Yao Huei; Yang, Pei Ming; Chuah, Qiu Yu; Lee, Yi Jang; Hsieh, Yi Fen; Peng, Chih Wen; Chiu, Shu Jun.

In: Autophagy, Vol. 10, No. 7, 2014, p. 1212-1228.

Research output: Contribution to journalArticle

Huang, Yao Huei ; Yang, Pei Ming ; Chuah, Qiu Yu ; Lee, Yi Jang ; Hsieh, Yi Fen ; Peng, Chih Wen ; Chiu, Shu Jun. / Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells. In: Autophagy. 2014 ; Vol. 10, No. 7. pp. 1212-1228.
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