In summary, we provide the first evidence that FOSL2 facilitates TGF-β1-induced migration in NSCLC cells by interaction with Smad3 and thus promotes P300 binding to Smad3 and Smad3 acetylation by P300, events that may contribute to the development of NSCLC and suggest FOSL2 as a potential therapeutic target in NSCLC. Here, FOSL2 is linked to non-small cell lung carcinoma.