Radiation driven epithelial-mesenchymal transition is mediated by Notch signaling in breast cancer
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Rae-Kwon Kim1,*, Neha Kaushik1,*, Yongjoon Suh1, Ki-Chun Yoo1, Yan-Hong Cui1, Min-Jung Kim2, Hae-June Lee3, In-Gyu Kim4, Su-Jae Lee1
1Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea
2Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
3Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
4Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon, Korea
*These authors contributed equally to this work
Su-Jae Lee, email: email@example.com
Keywords: radiation, EMT, Notch signaling, interleukin-6, breast cancer
Received: May 23, 2016 Accepted: July 13, 2016 Published: July 23, 2016
Epithelial to mesenchymal transition (EMT) is developmental process associated with cancer metastasis. Here, we found that breast carcinoma cells adopt epithelial-to-mesenchymal transition (EMT) in response to fractionated-radiation. Importantly, we show that Notch signaling is highly activated in fractionally-irradiated tumors as compared to non-irradiated tumors that are accompanied by an EMT. Moreover, we uncovered the mechanism of Notch-driven EMT, in which Notch enhanced EMT through IL-6/JAK/STAT3 signaling axis in mammary tumor cells. Collectively, we present converging evidence from our studies that Notch2 is a critical mediator of radiation-induced EMT and responsible for induced malignant tumor growth.
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