Interleukin 6-triggered ataxia-telangiectasia mutated kinase activation facilitates epithelial-to-mesenchymal transition in lung cancer by upregulating vimentin expression.

Abstract

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-κB 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.

• Authors: Yi Na Jiang, Xiao Yan Ni, Hong Qiong Yan, Lei Shi, Nan Nan Lu, Yi Nan Wang, Qing Li, Feng Guang Gao
• Journal: Experimental cell research (Exp Cell Res) Vol. 381 Issue 2 Pg. 165-171 (08 15 2019) ISSN: 1090-2422 [Electronic] United States
• PMID: 31100307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-6
• Vimentin
• ATM protein, human
• Ataxia Telangiectasia Mutated Proteins

Topics

• A549 Cells
• Animals
• Ataxia Telangiectasia Mutated Proteins (genetics, metabolism)
• Cell Line, Tumor
• Enzyme Activation (drug effects)
• Epithelial-Mesenchymal Transition (drug effects, genetics)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Interleukin-6 (pharmacology)
• Lung Neoplasms (genetics, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Metastasis
• Small Cell Lung Carcinoma (genetics, metabolism, pathology)
• Transcriptional Activation (drug effects, genetics)
• Vimentin (genetics, metabolism)