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FOSL2 positively regulates TGF-β1 signalling in non-small cell lung cancer
Junfeng Wang1, Dawei Sun1, Yanbo Wang1
1The Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
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.
Insights
Fos-related antigen 2 (FOSL2) is regulated by TGF-β1 and aids cancer cell migration. FOSL2 interacts with Smad3, suggesting it as a therapeutic target for non-small cell lung cancer (NSCLC).
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Fos-related antigen 2 (FOSL2), an AP-1 transcription factor, is implicated in various biological and disease processes.
- Limited knowledge exists regarding the regulatory pathways of FOSL2 expression and its functional mechanisms.
Purpose of the Study:
- To investigate the regulation of FOSL2 by TGF-β1.
- To elucidate the role of FOSL2 in TGF-β1-induced cell migration.
- To explore the interaction between FOSL2 and Smad3 in non-small cell lung cancer (NSCLC).
Main Methods:
- Investigated FOSL2 regulation by TGF-β1.
- Assessed FOSL2's requirement in TGF-β1-induced migration.
- Performed in vitro and in vivo interaction studies between FOSL2 and Smad3.
- Examined P300 binding and Smad3 acetylation.
- Correlated FOSL2 and activated Smad3 expression in NSCLC patient samples.
Main Results:
- FOSL2 expression is regulated by TGF-β1.
- FOSL2 is essential for TGF-β1-induced cell migration.
- FOSL2 interacts with Smad3, enhancing TGF-β1 signaling.
- FOSL2 promotes P300-mediated Smad3 acetylation.
- FOSL2 expression correlates with activated Smad3 in NSCLC.
Conclusions:
- FOSL2 facilitates TGF-β1-induced migration in NSCLC through Smad3 interaction.
- FOSL2 represents a potential therapeutic target for NSCLC.
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