ERBIN limits epithelial cell plasticity via suppression of TGF-β signaling

Li, C.; Zon, G. van der; Dijke, P. ten; Shen, T. (2025)

Article / Letter to editor

ERBIN acts as a negative regulator of the epidermal growth factor receptor (EGFR) and transforming growth factor-beta (TGF-beta)/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-beta-induced EMT in NMuMG breast and in A549 lung adenocarcinoma cell lines. ERBIN inhibits TGF-beta/SMAD-dependent gene expression and also interferes with TGF-beta-induced extracellular signal-regulated kinase (ERK) phosphorylation. Moreover, when the TGF-beta type I receptor kinase activity is inhibited, the mesenchymal state of ERBIN-depleted A549 cells is reduced. Pharmacological inhibition of TGF-beta 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-beta and EGFR signaling pathways.

• epidermal growth factor receptor
• epithelial-to-mesenchymal transition
• ERBIN
• extracellular signal-regulated kinase
• signal transduction
• transforming growth factor-beta

• All authors: Li, C.; Zon, G. van der; Dijke, P. ten; Shen, T.
• Date: 2025-07-20
• Journal: FEBS Letters
• Volume: 599
• Issue: 21
• Pages: 3103 - 3112
• DOI: doi:10.1002/1873-3468.70121