期刊
JOURNAL OF BIOCHEMISTRY
卷 151, 期 2, 页码 205-216出版社
OXFORD UNIV PRESS
DOI: 10.1093/jb/mvr136
关键词
EMT; lung adenocarcinoma; NF kappa B; TGF-beta; TNF-alpha
资金
- KAKENHI [22112002]
- Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) [22790750]
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [22590283, 22790750] Funding Source: KAKEN
Cancer cells undergo epithelial-mesenchymal transition (EMT) during invasion and metastasis. Although transforming growth factor-beta (TGF-beta) and pro-inflammatory cytokines have been implicated in EMT, the underlying molecular mechanisms remain to be elucidated. Here, we studied the effects of proinflammatory cytokines derived from the mouse macrophage cell line RAW 264.7 on TGF-beta-induced EMT in A549 lung cancer cells. Co-culture and treatment with conditioned medium of RAW 264.7 cells enhanced a subset of TGF-beta-induced EMT phenotypes in A549 cells, including changes in cell morphology and induction of mesenchymal marker expression. These effects were increased by the treatment of RAW 264.7 cells with lipopolysaccharide, which also induced the expression of various proinflammatory cytokines, including TNF-alpha and IL-1 beta. The effects of conditioned medium of RAW 264.7 cells were partially inhibited by a TNF-alpha neutralizing antibody. Dehydroxy methyl epoxyquinomicin, a selective inhibitor of NF kappa B, partially inhibited the enhancement of fibronectin expression by TGF-beta, TNF-alpha, and IL-1 beta, but not of N-cadherin expression. Effects of other pharmacological inhibitors also suggested complex regulatory mechanisms of the TGF-beta-induced EMT phenotype by TNF-alpha stimulation. These findings provide direct evidence of the effects of RAW 264.7-derived TNF-alpha on TGF-beta-induced EMT in A549 cells, which is transduced in part by NF kappa B signalling.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据