Interleukin 6 trigged ataxia-telangiectasia mutated activation facilitates lung cancer metastasis via MMP-3/MMP-13 up-regulation

Yi Na Jiang; Hong Qiong Yan; Xiao Bo Huang; Yi Nan Wang; Qing Li; Feng Guang Gao

doi:10.18632/oncotarget.5825

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Research Papers:

Interleukin 6 trigged ataxia-telangiectasia mutated activation facilitates lung cancer metastasis via MMP-3/MMP-13 up-regulation

Yi Na Jiang, Hong Qiong Yan, Xiao Bo Huang, Yi Nan Wang, Qing Li and Feng Guang Gao _

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Oncotarget. 2015; 6:40719-40733. https://doi.org/10.18632/oncotarget.5825

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Abstract

Yi Na Jiang1,*, Hong Qiong Yan1,*, Xiao Bo Huang1, Yi Nan Wang1, Qing Li1, Feng Guang Gao1,2

1Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, People's Republic of China

2State Key Laboratory of Oncogenes and Related Genes, Shang Hai Jiao Tong University, Shanghai 200032, People's Republic of China

*These authors have contributed equally to this work

Correspondence to:

Qing Li, e-mail: [email protected]

Feng Guang Gao, e-mail: [email protected]

Keywords: ataxia-telangiectasia mutated, interleukin 6, lung cancer, metastasis, matrix metalloproteinases

Received: May 20, 2015 Accepted: September 23, 2015 Published: October 22, 2015

ABSTRACT

Our previous studies show that the phosphorylation of ataxia-telangiectasia mutated (ATM) induced by interleukin 6 (IL-6) treatment contributes to multidrug resistance formation in lung cancer cells, but the exact role of ATM activation in IL-6 increased metastasis is still elusive. In the present study, matrix metalloproteinase-3 (MMP-3) and MMP-13 were firstly demonstrated to be involved in IL-6 correlated cell migration. Secondly, IL-6 treatment not only increased MMP-3/MMP-13 expression but also augmented its activities. Thirdly, the inhibition of ATM phosphorylation efficiently abolished IL-6 up-regulating MMP-3/MMP-13 expression and increasing abilities of cell migration. Most importantly, the in vivo test showed that the inhibition of ATM abrogate the effect of IL-6 on lung cancer metastasis via MMP-3/MMP-13 down-regulation. Taken together, these findings demonstrate that IL-6 inducing ATM phosphorylation increases the expression of MMP-3/MMP-13, augments the abilities of cell migration, and promotes lung cancer metastasis, indicating that ATM is a potential target molecule to overcome IL-6 correlated lung cancer metastasis.

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Research Papers:

Interleukin 6 trigged ataxia-telangiectasia mutated activation facilitates lung cancer metastasis via MMP-3/MMP-13 up-regulation

Abstract