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, and Shu-Jun Chiu1

 Autophagy, 2014. 10(7): p. 1212-28

Speaker: Cheng-Hao Chen (陳正豪)                            Time: 15:00~16:00, Sep 16, 2015

Commentator: Dr. Hsiao-Sheng Liu (劉校生老師)     Place: Room 601

Abstract:

Radiotherapy is one of the therapeutic choices for cancer treatment. Radiation induces several cellular effects ranging from DNA damage, growth arrest, apoptosis and senescence. Senescence is a defense mechanism in suppressing the proliferation of the cancer cells. In previous studies, it is been demonstrated that radiation can trigger the cellular senescence in order to inhibit the proliferation of breast cancer cells.[1] However, these senescent cells in turn release senescence-associated secretory phenotypes (SASPs) which further induce the migration and invasion of unirradiated-neighboring cells, known as the bystander effects.[2] Emerging evidences indicate that autophagy participates in senescence progression. Nevertheless, the role of autophagy in radiation-induced senescence and bystander effects in breast cancer cells has not yet been addressed. The authors found that autophagy was involved in radiation-induced senescence, and inhibition of autophagy triggered apoptosis instead of senescence in irradiated-breast cancer cells. In addition, senescent cancer cells secreted colony stimulating factor 2 (CSF2) and further promoted the bystander effects in unirradiated-neighboring breast cancer cells and human umbilical vein endothelial cells (HUVECs) through JAK2-STAT3 signaling pathway. However, radiation-triggered bystander effects were correlated to the downregulation of endogenous autophagy in neighboring cells; induction of autophagy by rapamycin treatment reduced the radiation-induced bystander effects. Taken together, autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells.

References:

1.         Chen, W.S., et al., Depletion of securin induces senescence after irradiation and enhances radiosensitivity in human cancer cells regardless of functional p53 expression. Int J Radiat Oncol Biol Phys, 2010. 77(2): p. 566-74.

2.         Yu, Y.C., et al., Radiation-induced senescence in securin-deficient cancer cells promotes cell invasion involving the IL-6/STAT3 and PDGF-BB/PDGFR pathways. Sci Rep, 2013. 3: p. 1675.