Radiation-induced senescence in securin-deficient cancer cells promotes cell invasion involving the IL-6/STAT3 and PDGF-BB/PDGFR pathways
| Autor: | Qiu Yu Chuah, Chih Wen Peng, Yao Huei Huang, Shu Jun Chiu, Pei Ming Yang, Yi Jang Lee, Yi Chu Yu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Senescence
STAT3 Transcription Factor Angiogenesis Becaplermin Breast Neoplasms Biology Radiation Dosage Article Paracrine signalling Cell Line Tumor medicine Humans Neoplasm Invasiveness Receptors Platelet-Derived Growth Factor Multidisciplinary Interleukin-6 Cancer Cell migration Proto-Oncogene Proteins c-sis medicine.disease Neoplasm Proteins Endothelial stem cell Securin Cancer cell Cancer research Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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