TGFB1 and cancer: Indeed, in vivo experiments show that NR overexpression in PTEN −/− prostatic epithelium leads to increased cancer cell proliferation and invasiveness; these effects are a consequence of the direct binding and sequestration of SMAD4 by COUP-TFII that causes the loss of the TGF-β signal and the reduction of TGF-β-induced growth barrier [169].