# ERBIN limits epithelial cell plasticity via suppression of TGF‐β signaling

## TL;DR

ERBIN suppresses cell transformation linked to cancer by inhibiting TGF-β and EGFR signaling pathways.

## Contribution

ERBIN is identified as a key suppressor of EMT through coordinated inhibition of TGF-β and EGFR signaling.

## Key findings

- ERBIN inhibits TGF-β-induced EMT in breast and lung cancer cell lines.
- ERBIN suppresses TGF-β/SMAD signaling and reduces ERK phosphorylation.
- Pharmacological inhibition of TGF-β and EGFR signaling counteracts EMT in ERBIN-depleted cells.

## Abstract

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.

In breast and lung cancer patients, low ERBIN expression correlates with poor clinical outcomes. Here, we show that ERBIN inhibits TGF‐β‐induced epithelial‐to‐mesenchymal transition in NMuMG breast and A549 lung adenocarcinoma cell lines. ERBIN suppresses TGF‐β/SMAD signaling and reduces TGF‐β‐induced ERK phosphorylation. Pharmacological inhibition of TGF‐β receptor and EGFR signaling mitigates the enhanced EMT and migration in ERBIN‐depleted A549 cells.