Radiation driven epithelial-mesenchymal transition is mediated by Notch signaling in breast cancer

Abstract

// Rae-Kwon Kim 1, * , Neha Kaushik 1, * , Yongjoon Suh 1 , Ki-Chun Yoo 1 , Yan-Hong Cui 1 , Min-Jung Kim 2 , Hae-June Lee 3 , In-Gyu Kim 4 , Su-Jae Lee 1 1 Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea 2 Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea 3 Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul, Korea 4 Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon, Korea * These authors contributed equally to this work Correspondence to: Su-Jae Lee, email: sj0420@hanyang.ac.kr Keywords: radiation, EMT, Notch signaling, interleukin-6, breast cancer Received: May 23, 2016      Accepted: July 13, 2016      Published: July 23, 2016 ABSTRACT 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.