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

TL;DR

This paper reviews how integrins and TGF-β work together to drive breast cancer metastasis and suggests targeting their interaction as a potential treatment.

Contribution

The paper provides a comprehensive review of the integrin-TGF-β axis's role in breast cancer progression and therapeutic targeting.

Findings

Integrins αvβ3, αvβ6, and β1 modulate TGF-β signaling and promote EMT and metastasis.

The integrin-TGF-β axis influences immune evasion, angiogenesis, and ECM remodeling.

Targeting this axis with inhibitors or combination therapies may reduce metastasis.

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.

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