title: Interleukin 6 trigged ataxia-telangiectasia mutated activation facilitates lung cancer metastasis via MMP-3/MMP-13 up-regulation.
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.
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, People's Republic of China.
authors.forename: Yi Na
authors.initials: YN
authors.lastname: Jiang
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, People's Republic of China.
authors.forename: Hong Qiong
authors.initials: HQ
authors.lastname: Yan
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, People's Republic of China.
authors.forename: Xiao Bo
authors.initials: XB
authors.lastname: Huang
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, People's Republic of China.
authors.forename: Yi Nan
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, People's Republic of China.|State Key Laboratory of Oncogenes and Related Genes, Shang Hai Jiao Tong University, Shanghai 200032, People's Republic of China.
authors.forename: Feng Guang
authors.initials: FG
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D064007:Ataxia Telangiectasia Mutated Proteins; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3
keywords: ataxia-telangiectasia mutated; interleukin 6; lung cancer; matrix metalloproteinases; metastasis