Transforming growth factor-β and integrins: key players in EMT and breast cancer progression

Abstract

In advanced breast cancer, the integrin-TGF-β axis moves from a tumor-suppressive to a pro-metastatic state and is central to breast cancer metastasis. We review how integrins, especially αvβ3, αvβ6, and β1, serve as critical modulators of TGF-β signaling and play a key role in epithelial-to-mesenchymal transition (EMT), immune evasion, angiogenesis, and ECM remodeling. In addition to activating latent TGFβ, these integrins also function as downstream effectors that fuel EMT and tumor progression through a feedback loop. Integrins function mechanistically to promote cytoskeletal reorganization, ECM degradation, and tumor cell motility, and TGF-β signaling influences integrin expression and activity. Targeting this axis is explored as a therapeutic approach to reduce metastasis and improve patient outcomes, and the potential of integrin inhibitors, TGFβ pathway blockers, and combination therapies are discussed. This review highlights the need for novel interventions to disrupt this axis by elucidating the interplay between integrins and TGF-β.