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

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.

SMC1A is associated with radioresistance in prostate cancer and acts by regulating epithelial‐mesenchymal transition and cancer stem‐like properties

“…Radiotherapy kills the cancer cells directly by causing DNA damage, but radiation also causes the generation of reactive oxygen species (ROS) which are indirectly involved in DNA damage . Moreover, RT promotes metastasis and invasion of cancer cells and is involved in epithelial‐mesenchymal transition (EMT) . Therefore, attenuating EMT pathways may improve the efficacy of radiotherapy.…”

“…Therefore, attenuating EMT pathways may improve the efficacy of radiotherapy. Unfortunately, currently known anti‐metastatic or anti‐angiogenic inhibitors have limitations because of their acute toxicity and drug resistance …”

“…[11][12][13] Moreover, RT promotes metastasis and invasion of cancer cells and is involved in epithelial-mesenchymal transition (EMT). [14][15][16][17][18] Therefore, attenuating EMT pathways may improve the efficacy of radiotherapy. Unfortunately, currently known anti-metastatic or anti-angiogenic inhibitors have limitations because of their acute toxicity and drug resistance.…”

“…Unfortunately, currently known anti-metastatic or anti-angiogenic inhibitors have limitations because of their acute toxicity and drug resistance. [15][16][17][18] Here, we describe that structural maintenance of chromosome-1 (SMC1A), a member of cohesin and one of the major target substrates of ATM kinase is overexpressed in prostate cancer. It is also known to be overexpressed and associated with tumor metastasis in breast, lung, glioma, and colorectal cancers.…”

The ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy

“…Clinically used, radiation treatment not only kills breast cancer cells and prolongs survival in breast cancer but also triggers exposed residual cells that are not killed to undergo EMT, to start migrating, and to synthesize increased amounts of autocrine growth factor, GM-CSF 49. Radiation also increases IL-6, migration, and EMT markers in murine and human breast cancer cell lines 50. The subject of radiation-induced EMT and radiation-induced increase in CTCs was recently reviewed by Lee et al51…”