FOSL2 Positively Regulates TGF-β1 Signalling in Non-Small Cell Lung Cancer

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-beta 1 and that FOSL2 is required for TGF-beta 1-induced migration. We demonstrate that FOSL2 interacts with Smad3 in vitro and in vivo and thus up-regulates TGF-beta 1-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-beta 1-induced migration by interaction with Smad3 in NSCLC and suggests FOSL2 as a potential therapeutic target for NSCLC.