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

Author(s):
Li, C.; Zon, G. van der; Dijke, P. ten (0000-0002-7234-342X); Shen, T.
Published
2025
Publication type
Article / Letter to editor

Abstract

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 receptorepithelial-to-mesenchymal transitionERBINextracellular signal-regulated kinasesignal transductiontransforming growth factor-beta
Date issued
2025-07-20
Language
English
Publisher
WILEY
Is part of
FEBS Letters (2025), Vol. 599, no. 21, p. 3103-3112
hdl
1887/4290176
doi
10.1002/1873-3468.70121