title: Suppression of radiation-induced migration of non-small cell lung cancer through inhibition of Nrf2-Notch Axis.
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.
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China.|University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Institute of Gansu Medical Science Research, Lanzhou 730000, China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Mao
authors.affiliation: South China Normal University, Guangzhou 510642, China.
authors.forename: Ruoshui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Northwest Normal University, Lanzhou 730000, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China.|University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Lan Zhou University, Lanzhou 730000, China.
authors.forename: Jinzhou
authors.initials: J
authors.lastname: Tang
authors.affiliation: Gansu Wuwei Institute of Medical Sciences, Gansu Province, Wuwei 733000, China.
authors.forename: Yancheng
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Gansu Wuwei Institute of Medical Sciences, Gansu Province, Wuwei 733000, China.
authors.forename: Yanshan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|Gansu Wuwei Institute of Medical Sciences, Gansu Province, Wuwei 733000, China.|Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*; D014965:X-Rays
chemical_list: D051267:NF-E2-Related Factor 2; D051880:Receptors, Notch; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: EMT; NSCLC; Notch1; Nrf2; ionizing radiation