Year: 2023
Type: article
Abstract: EGFR-ERK signaling controls cell cycle progression during development, homeostasis, and disease. While EGF ligand and mechanical inputs can activate EGFR-ERK signaling, the molecules linking mechanical force to this axis have remained mysterious. We previously found that stretch promotes mitosis via the stretch-activated ion channel Piezo1 and ERK signaling. Here, we show that Piezo1 provides the missing link between mechanical signals and EGFR-ERK activation. While both EGF- and Piezo1-dependent activation trigger clathrin-mediated EGFR endocytosis and ERK activation, EGF relies on canonical tyrosine autophosphorylation, whereas Piezo1 involves Src-p38 kinase-dependent serine phosphorylation. In addition, unlike EGF, ex vivo lung slices treated with Piezo1 agonist promoted cell cycle re-entry via nuclear ERK, AP-1 (FOS and JUN), and YAP accumulation, typical of regenerative and malignant signaling. Our results suggest that mechanical activation via Piezo1, Src, and p38 may be more relevant to controlling repair, regeneration, and cancer growth than tyrosine kinase signaling via canonical EGF signaling, suggesting an alternative therapeutic approach.
Source: Science Advances
Authors: Carlos Pardo-Pastor, Jody Rosenblatt
Institution: King's College London
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: The role of epithelial cell extrusion in asthma, G1648405351, G2327867857, G3053397744, Regulation of epithelial and endothelial cell-cell junctions by mechanical forces, G434337789, Mechanical regulation of cell migration by Piezo1 and its implications in epithelial cell turnover, The role of epithelial cell extrusion in asthma, Mobility Support Centre Macedonia
OpenAlex ID: W4387092065