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

// Yi Na Jiang 1, * , Hong Qiong Yan 1, * , Xiao Bo Huang 1 , Yi Nan Wang 1 , Qing Li 1 , Feng Guang Gao 1, 2 1 Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, People's Republic of China 2 State 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: sunnymaylq@hotmail.com Feng Guang Gao, e-mail: gfengguang@xmu.edu.cn 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.