Oncotarget

Research Papers:

Suppression of radiation-induced migration of non-small cell lung cancer through inhibition of Nrf2-Notch Axis

Qiuyue Zhao, Aihong Mao, Ruoshui Guo, Liping Zhang, Jiawei Yan, Chao Sun, Jinzhou Tang, Yancheng Ye, Yanshan Zhang and Hong Zhang _

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Oncotarget. 2017; 8:36603-36613. https://doi.org/10.18632/oncotarget.16622

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Abstract

Qiuyue Zhao1,2,4,5, Aihong Mao6, Ruoshui Guo7, Liping Zhang8, Jiawei Yan1,2,4,5, Chao Sun1,2,4, Jinzhou Tang9, Yancheng Ye3, Yanshan Zhang3 and Hong Zhang1,2,3,4

1Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China

2Key Laboratory of Heavy Ion Radiation and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China

3Gansu Wuwei Institute of Medical Sciences, Gansu Province, Wuwei 733000, China

4Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China

5University of Chinese Academy of Sciences, Beijing 100039, China

6Institute of Gansu Medical Science Research, Lanzhou 730000, China

7South China Normal University, Guangzhou 510642, China

8Northwest Normal University, Lanzhou 730000, China

9Lan Zhou University, Lanzhou 730000, China

Correspondence to:

Hong Zhang, email: zhangh@impcas.ac.cn

Keywords: Nrf2, ionizing radiation, Notch1, EMT, NSCLC

Received: January 23, 2017     Accepted: March 09, 2017     Published: March 28, 2017

ABSTRACT

Nuclear factor E2 related factor 2 (Nrf2) is a transcription factor that is associated with tumor growth and resistance to radiation. The canonical Notch signaling pathway is also crucial for maintaining non-small cell lung cancer (NSCLC). Aberrant Nrf2 and Notch signaling has repeatedly been showed to facilitate metastasis of NSCLC. Here, we show that radiation induce Nrf2 and Notch1 expression in NSCLC. Knockdown of Nrf2 enhanced radiosensitivity of NSCLC and reduced epithelial-to-mesenchymal transition. Importantly, we found that knockdown of Nrf2 dramatically decreased radiation-induced NSCLC invasion and significantly increased E-cadherin, but reduced N-cadherin and matrix metalloproteinase (MMP)-2/9 expression. We found that Notch1 knockdown also upregulated E-cadherin and suppressed N-cadherin expression. Nrf2 contributes to NSCLC cell metastatic properties and this inhibition correlated with reduced Notch1 expression. These results establish that Nrf2 and Notch1 downregulation synergistically inhibit radiation-induced migratory and invasive properties of NSCLC cells.


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