Radiation promotes malignant phenotypes through SRC in breast cancer cells.
Bottom Line: However, the molecular mechanisms underlying radiation-induced cancer progression remain obscure.Importantly, radiation-activated SRC induced SLUG expression and caused epithelial-mesenchymal cell transition through phosphatidylinositol 3-kinase/protein kinase B and p38 MAPK signaling.In addition, downregulation of SRC also abolished radiation-acquired resistance of breast cancer cells to anticancer agents such as cisplatin, etoposide, paclitaxel, and IR.
Affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.Show MeSH
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Mentions: As CSCs are reported to be resistant to chemo- and radiotherapy,13,14 we next examined whether irradiation increases the resistance of cancer cells to anticancer treatments through activation of SRC. To this end, breast cancer cells were exposed to fractionated radiation, and on the following day cells were treated with anticancer agents cisplatin, etoposide, or paclitaxel. When cell death was analyzed by FACS, we found that breast cancer cells exposed to fractionated radiation showed more resistance to cisplatin, etoposide, and paclitaxel compared to non-irradiated cells (Fig.5a–c). To examine whether pretreatment with fractionated radiation also confers radio-resistance on cancer cells, MCF7 cells were exposed to fractionated radiation and followed exposure to IR (10 Gy). Consistently, we observed that pretreatment with fractionated irradiation caused breast cancer cells to become more resistant to IR (10 Gy), compared to non-irradiated control cells (Fig.5d). However, pretreatment with siRNA targeting SRC prevented breast cancer cells from acquiring radiation-induced resistance to cisplatin, etoposide, paclitaxel, and IR (Fig.5). Taken together, these results suggest that radiation-activated SRC is necessary for the acquisition of resistance to chemo- and radiotherapy in breast cancer cells.
Affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.