Transforming growth factor beta 1-induced epithelial-mesenchymal transition pathway (TGF-β1-EMT)

The TGF-β1-induced epithelial-mesenchymal transition (EMT) pathway is a complex signaling cascade where epithelial cells lose their polarity and cell-cell adhesion, gaining migratory and invasive properties characteristic of mesenchymal cells (Lamouille et al., 2014, Nature Reviews Molecular Cell Biology). This process is primarily initiated by the binding of Transforming Growth Factor-beta 1 (TGF-β1) to its cognate receptors (TGFBR1 and TGFBR2), triggering both Smad-dependent and Smad-independent (e.g., MAPK, PI3K/Akt) signaling pathways (Meng et al., 2016, Nature Reviews Nephrology). In physiological contexts, this pathway is essential for embryonic development and wound healing; however, its dysregulation is a hallmark of various pathologies, most notably cancer metastasis and organ fibrosis (Akhurst, 2017, Nature Reviews Drug Discovery). In oncology, TGF-β1-induced EMT promotes the transition of tumor cells into a more aggressive, chemoresistant, and metastatic phenotype. Therapeutic strategies targeting this pathway include small molecule inhibitors of the TGF-beta receptor kinases and monoclonal antibodies that neutralize the TGF-β ligands (Herbertz et al., 2015, Drug Design, Development and Therapy). Despite its potential, targeting this pathway remains challenging due to the pleiotropic nature of TGF-β signaling, which can act as a tumor suppressor in early-stage cancers and a promoter in late-stage disease, leading to concerns regarding systemic toxicity and off-target effects.

Other names

TGF-beta 1-mediated EMTTGFB1-EMT signaling cascadeTGF-β-induced epithelial to mesenchymal transition

Inhibition of TGF-beta receptor type I (ALK5) kinase activity, neutralization of TGF-beta ligands, or blockade of TGF-beta receptor II binding to prevent downstream Smad and non-Smad signaling activation (Akhurst, 2017, Nature Reviews Drug Discovery).