SMAD4 and neoplasm: Consistent with the anti-metastatic activity of BMP4, constitutively active BMPR1a in SMAD4 positive tumors displayed a significant reduction in metastasis to lung, liver and spine (Fig. 4d,e), however, in the absence of SMAD4, the suppression of metastasis was largely abrogated (Fig. 4d,e), indicating that SMAD4 activity is required for inhibition of metastasis following tumor cell-specific BMP signalling.