SMAD4 and non-small cell lung carcinoma: Additionally, Bydoun et al. determined that, upon EMT induction by TGFβ1, PAI-1 was significantly upregulated in A549 non-small cell lung carcinoma (NSCLC) cells and this effect was modulated via FOXC2-mediated PI3K signaling as well as SMAD4-dependent TGFβ1 signaling [143].