The major findings of our study are: a) PITX2 up-regulates the expression of ligand genes of TGF-β superfamily, TGFB and INHBA followed by induction of SMAD2/3-dependent TGF-β signalling pathway; b) through the activation of TGF-β pathway, PITX2 regulates the expression of genes that enhances invasion and EMT of ovarian cancer cells; c) This is the first report to show the direct involvement of activin-A, the homodimer form of INHBA, in promoting invasion and EMT of both non-cancerous and cancerous cells. The gene discussed is SMAD2; the disease is ovarian cancer.