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 cancer.