EGFR and HER2 activate rigidity sensing only on rigid matrices.
Nat Mater
; 16(7): 775-781, 2017 07.
Article
en En
| MEDLINE
| ID: mdl-28459445
ABSTRACT
Epidermal growth factor receptor (EGFR) interacts with integrins during cell spreading and motility, but little is known about the role of EGFR in these mechanosensing processes. Here we show, using two different cell lines, that in serum- and EGF-free conditions, EGFR or HER2 activity increase spreading and rigidity-sensing contractions on rigid, but not soft, substrates. Contractions peak after 15-20 min, but diminish by tenfold after 4 h. Addition of EGF at that point increases spreading and contractions, but this can be blocked by myosin-II inhibition. We further show that EGFR and HER2 are activated through phosphorylation by Src family kinases (SFK). On soft surfaces, neither EGFR inhibition nor EGF stimulation have any effect on cell motility. Thus, EGFR or HER2 can catalyse rigidity sensing after associating with nascent adhesions under rigidity-dependent tension downstream of SFK activity. This has broad implications for the roles of EGFR and HER2 in the absence of EGF both for normal and cancerous growth.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Movimiento Celular
/
Receptor ErbB-2
/
Mecanotransducción Celular
/
Fibroblastos
/
Receptores ErbB
Límite:
Animals
Idioma:
En
Revista:
Nat Mater
Asunto de la revista:
CIENCIA
/
QUIMICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos