Journal
EXPERIMENTAL CELL RESEARCH
Volume 381, Issue 2, Pages 165-171Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2019.05.011
Keywords
Ataxia-telangiectasia mutated; Interleukin 6; Lung cancer; Epithelial-mesenchymal transition; Vimentin
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Funding
- State Key Laboratory of Oncogenes and Related Genes [90-14-05]
- National Natural Science Foundation of China [81273203, 81201275, 81771669]
- Natural Science Foundation of Fujian Province of China [2015J01353]
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Matrix metalloproteinases (MMPs) and the epithelial-mesenchymal transition (EMT) contribute to metastasis. As shown in our previous studies, interleukin-6 (IL-6) induces ATM phosphorylation to increase MMP expression and metastasis in lung cancer. However, the exact roles of ATM activation in the IL-6-induced epithelial-mesenchymal transition and lung cancer metastasis are currently unclear. Here, ATM phosphorylation exerts its pro-metastatic effect via vimentin-mediated epithelial-mesenchymal transition, which was supported by the evidence described below. Firstly, IL-6 treatment increases vimentin expression via the ATM-NF-kappa B pathway. Second, ATM inactivation not only abolishes IL-6-induced increases in vimentin expression but also inhibits IL-6-induced nest formation in a xenograft lung metastasis model. Moreover, close positive correlations were observed between ATM phosphorylation and vimentin upregulation, IL-6 levels and metastasis in lung cancer specimens. Hence, ATM modulates vimentin expression to facilitate IL-6-induced epithelial-mesenchymal transition and metastasis in lung cancer, indicating that ATM and vimentin might be potential therapeutic targets for inflammation-associated lung cancer metastasis.
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