Radiation promotes malignant phenotypes through SRC in breast cancer cells

Title
Radiation promotes malignant phenotypes through SRC in breast cancer cells
Author
이수재
Keywords
resistance to anticancer agents; epithelial-mesenchymal cell transition; Cancer stem cells; ionizing radiation; SRC
Issue Date
2015-01
Publisher
WILEY-BLACKWELL
Citation
CANCER SCIENCE, v. 106, NO 1, Page. 78-85
Abstract
Despite the fact that ionizing radiation (IR) is widely used as a standard treatment for breast cancer, much evidence suggests that IR paradoxically promotes cancer malignancy. However, the molecular mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that irradiation activates SRC signaling among SRC family kinase proteins, thereby promoting malignant phenotypes such as invasiveness, expansion of the cancer stem-like cell population, and resistance to anticancer agents in breast cancer cells. 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 agreement, either inhibition of SRC or downstream signaling of p38 MAPK or protein kinase B effectively attenuated radiation-induced epithelial-mesenchymal cell transition along with an increase in the cancer stem-like cell population. In addition, downregulation of SRC also abolished radiation-acquired resistance of breast cancer cells to anticancer agents such as cisplatin, etoposide, paclitaxel, and IR. Taken together, our findings suggest that combining radiotherapy with targeting of SRC might attenuate the harmful effects of radiation and enhance the efficacy of breast cancer treatment.
URI
http://hdl.handle.net/20.500.11754/21314http://onlinelibrary.wiley.com/doi/10.1111/cas.12574/full
ISSN
1347-9032
DOI
10.1111/cas.12574
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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