The results reported here suggest that TMEPAI appears to have a dynamic role in regulation of TGF- β canonical and non-canonical signaling and help to explain how increased TMEPAI protein subverts normally tumor suppressive TGF-β signaling to promote TGF-β dependent proliferation of triple negative breast cancer cells and enhance their metastatic propensity. Here, PMEPA1 is linked to triple-negative breast carcinoma.