The cooperative actions of TMEPAI to decrease growth suppressive Smad signaling together with TMEPAI mediated effects on PTEN-Akt to promote growth and metastasis constitute a signaling pathology fundamentally altered from the normal state that may explain the underlying reason for TGF-β mediated tumor promotion in a large number of triple-negative breast cancers. The gene discussed is AKT1; the disease is triple-negative breast carcinoma.