title: Radiation-induced senescence in securin-deficient cancer cells promotes cell invasion involving the IL-6/STAT3 and PDGF-BB/PDGFR pathways.
abstract: Securin overexpression correlates with poor prognosis in various tumours. We have previously shown that securin depletion promotes radiation-induced senescence and enhances radiosensitivity in human cancer cells. However, the underlying molecular mechanisms and the paracrine effects remain unknown. In this study, we showed that radiation induced senescence in securin-deficient human breast cancer cells involving the ATM/Chk2 and p38 pathways. Conditioned medium (CM) from senescent cells promoted the invasion and migration of non-irradiated cancer and endothelial cells. Cytokine assay analysis showed the up-regulation of various senescence-associated secretory phenotypes (SASPs). The IL-6/STAT3 signalling loop and platelet-derived growth factor-BB (PDGF-BB)/PDGF receptor (PDGFR) pathway were important for CM-induced cell migration and invasion. Furthermore, CM promoted angiogenesis in the chicken chorioallantoic membrane though the induction of IL-6/STAT3- and PDGF-BB/PDGFR-dependent endothelial cell invasion. Taken together, our results provide the molecular mechanisms for radiation-induced senescence in securin-deficient human breast cancer cells and for the SASP responses.
authors.affiliation: Department of Life Sciences, Tzu Chi University, Hualien, Taiwan, R.O.C.
authors.forename: Yi-Chu
authors.initials: YC
authors.lastname: Yu
authors.forename: Pei-Ming
authors.initials: PM
authors.lastname: Yang
authors.forename: Qiu-Yu
authors.initials: QY
authors.lastname: Chuah
authors.forename: Yao-Huei
authors.initials: YH
authors.lastname: Huang
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Peng
authors.forename: Yi-Jang
authors.initials: YJ
authors.lastname: Lee
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Chiu
mesh_terms: D000077214:Becaplermin; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D011829:Radiation Dosage; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D064249:Securin; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D009363:Neoplasm Proteins; D020574:Proto-Oncogene Proteins c-sis; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor