biostudies-literatureLi CChina Scholarship CouncilZonMwZonMw grant3103-3112https://www.ebi.ac.uk/biostudies/studies/S-EPMC12599596biostudies-literatureUnknown599(21)ERBIN acts as a negative regulator of the epidermal growth factor receptor (EGFR) and transforming growth factor-β (TGF-β)/SMAD signaling pathways that play a role in epithelial-to-mesenchymal transition (EMT). However, the role of ERBIN in EMT is poorly understood. Our results show that ERBIN inhibits TGF-β-induced EMT in NMuMG breast and in A549 lung adenocarcinoma cell lines. ERBIN inhibits TGF-β/SMAD-dependent gene expression and also interferes with TGF-β-induced extracellular signal-regulated kinase (ERK) phosphorylation. Moreover, when the TGF-β type I receptor kinase activity is inhibited, the mesenchymal state of ERBIN-depleted A549 cells is reduced. Pharmacological inhibition of TGF-β receptor and EGFR signaling counteracts increased EMT and migration in A549 ERBIN-depleted cells. Our findings identify ERBIN as a key suppressor of EMT through coordinated inhibition of TGF-β and EGFR signaling pathways.FEBS lettersERBIN limits epithelial cell plasticity via suppression of TGF-β signaling.PMC1259959609120012010061Ten Dijke PLi Cvan der Zon GShen TfalseERBIN limits epithelial cell plasticity via suppression of TGF-β signaling.ERBIN acts as a negative regulator of the epidermal growth factor receptor (EGFR) and transforming growth factor-β (TGF-β)/SMAD signaling pathways that play a role in epithelial-to-mesenchymal transition (EMT). However, the role of ERBIN in EMT is poorly understood. Our results show that ERBIN inhibits TGF-β-induced EMT in NMuMG breast and in A549 lung adenocarcinoma cell lines. ERBIN inhibits TGF-β/SMAD-dependent gene expression and also interferes with TGF-β-induced extracellular signal-regulated kinase (ERK) phosphorylation. Moreover, when the TGF-β type I receptor kinase activity is inhibited, the mesenchymal state of ERBIN-depleted A549 cells is reduced. Pharmacological inhibition of TGF-β receptor and EGFR signaling counteracts increased EMT and migration in A549 ERBIN-depleted cells. Our findings identify ERBIN as a key suppressor of EMT through coordinated inhibition of TGF-β and EGFR signaling pathways.2025-01-01T00:00:00Z2025 Nov2026-06-05T12:24:13.086Z2026-05-16T03:12:57.155ZS-EPMC125995964085986610.1002/1873-3468.70121