Ataxia-telangiectasia mutated activation mediates tumor necrosis factor-alpha induced MMP-13 up-regulation and metastasis in lung cancer cells.

ABSTRACT: Despite that ataxia-telangiectasia mutated (ATM) is involved in IL-6 promoted lung cancer chemotherapeutic resistance and metastasis, the exact role of ATM in tumor necrosis factor-alpha (TNF-α) increasing tumor migration is still elusive. In the present study, we demonstrated that TNF-α promoted lung cancer cell migration by up-regulation of matrix metalloproteinase-13 (MMP-13). Notably, by gene silencing or kinase inhibition, we proposed for the first time that ATM is a key up-stream regulator of TNF-α activated ERK/p38-NF-κB pathway. The existence of TNF-α secreted in autocrine or paracrine manner by components of tumor microenvironment highlights the significance of TNF-α in inflammation-associated tumor metastasis. Importantly, in vivo lung cancer metastasis test showed that ATM deple

SUBMITTER: Yan HQ 

PROVIDER: S-EPMC5308711 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature