期刊
ONCOTARGET
卷 8, 期 22, 页码 36603-36613出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.16622
关键词
Nrf2; ionizing radiation; Notch1; EMT; NSCLC
资金
- Key program of National Natural Science Foundation of China [U1432248, U1632270]
- Ministry of science and technology national key R D project [2016YFC0904600]
- National Natural Science Foundation of China [11665003]
- Scientific Technology Research Projects of Gansu Province [0702NKDA045, 0801NKDA001, 092NKDA034]
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-tomesenchymal 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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