Abstract
Fos-related antigen 2 (FRA-2/FOSL2) belongs to the AP-1 transcription factor family. Although FOSL2 has been shown to be involved in diverse physiological and pathological processes, very little is known about the signalling pathways that regulate FOSL2 expression and the mechanisms of FOSL2 function. Here, we show that FOSL2 expression is regulated by TGF-β1 and that FOSL2 is required for TGF-β1-induced migration. We demonstrate that FOSL2 interacts with Smad3 in vitro and in vivo and thus up-regulates TGF-β1-induced signalling responses. Mechanistically, FOSL2 promotes P300 binding to Smad3 and the acetylation of Smad3 by P300. Furthermore, we show that the expression of FOSL2 correlates with activated Smad3 expression in clinical non-small cell lung cancer (NSCLC) samples. In summary, the present study indicates that FOSL2 facilitates TGF-β1-induced migration by interaction with Smad3 in NSCLC and suggests FOSL2 as a potential therapeutic target for NSCLC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Carcinoma, Non-Small-Cell Lung / metabolism*
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Carcinoma, Non-Small-Cell Lung / mortality
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Movement / drug effects
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E1A-Associated p300 Protein / metabolism
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Fos-Related Antigen-2 / metabolism*
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Humans
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Kaplan-Meier Estimate
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Lung Neoplasms / metabolism*
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Lung Neoplasms / mortality
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Lung Neoplasms / pathology
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Signal Transduction
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Smad3 Protein / metabolism
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Transforming Growth Factor beta1 / metabolism*
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Transforming Growth Factor beta1 / pharmacology
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Tumor Cells, Cultured
Substances
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FOSL2 protein, human
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Fos-Related Antigen-2
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SMAD3 protein, human
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Smad3 Protein
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Transforming Growth Factor beta1
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E1A-Associated p300 Protein
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EP300 protein, human
Grants and funding
This work was supported by the National Natural Science Foundation of China (81172818; 81172215). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.