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

Rae-Kwon Kim,Hae-June Lee,In-Gyu Kim,Neha Kaushik,Yongjoon Suh,Su-Jae Lee,Ki-Chun Yoo,Min-Jung Kim,Yan-Hong Cui

doi:10.18632/oncotarget.10802

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.

Highlights

Most cancer deaths from breast cancer result from tumor recurrence following treatment of the primary tumor
When the protein levels of epithelialto-mesenchymal transition (EMT) transcription factors such as SNAIL, SLUG, ZEB1 and TWIST were investigated, irradiation was found to cause a strong increase of SLUG; other EMT transcription factors were not altered by irradiation in MCF7 breast cancer cells (Figure 1E)
These results suggest that radiation causes breast cancer cells to acquire migratory and invasive properties by inducing SLUG and thereby triggering the EMT program

Summary

Introduction

Most cancer deaths from breast cancer result from tumor recurrence following treatment of the primary tumor. The emergence of radio-resistance leads to the failure of radiotherapy and subsequently increases mortality frequently in patients [1] These consequences suggest that a subcellular fraction of radiation resistant tumor cells with potent tumorigenic activity is critical for re-growth [2,3,4]. To overcome these problems, determining the underlying molecular mechanisms associated with radiation-induced epithelialto-mesenchymal transition (EMT) will be helpful for breast cancer relapse predictions and would greatly improve the therapeutic approaches for this disease [5,6,7]. Undertaking this aim, we focused on epithelialto-mesenchymal transition (EMT) phenomenon in breast tumor cells

Methods

Results

Conclusion