TGF-β signaling is critical for promoting cancer metastasis, primarily via Smad-dependent regulation of the epithelial-mesenchymal transition; this study reveals that non-canonical TGF-β signaling stabilizes the E3 ubiquitin ligase FBXO3 to target ΔNp63α for degradation, resulting in downregulation of adhesion molecules and promotion of breast cancer metastasis. Here, TGFB1 is linked to breast carcinoma.