Orphan G protein-coupled receptor GPRC5A modulates integrin ß1-mediated epithelial cell adhesion.
Cell Adh Migr
; 11(5-6): 434-446, 2017 Sep 03.
Article
in En
| MEDLINE
| ID: mdl-27715394
ABSTRACT
G-Protein Coupled Receptor (GPCR), Class C, Group 5, Member A (GPRC5A) has been implicated in several malignancies. The underlying mechanisms, however, remain poorly understood. Using a panel of human cell lines, we demonstrate that CRISPR/Cas9-mediated knockout and RNAi-mediated depletion of GPRC5A impairs cell adhesion to integrin substrates collagens I and IV, fibronectin, as well as to extracellular matrix proteins derived from the Engelbreth-Holm-Swarm (EHS) mouse sarcoma (Matrigel). Consistent with the phenotype, knock-out of GPRC5A correlated with a reduced integrin ß1 (ITGB1) protein expression, impaired phosphorylation of the focal adhesion kinase (FAK), and lower activity of small GTPases RhoA and Rac1. Furthermore, we provide the first evidence for a direct interaction between GPRC5A and a receptor tyrosine kinase EphA2, an upstream regulator of FAK, although its contribution to the observed adhesion phenotype is unclear. Our findings reveal an unprecedented role for GPRC5A in regulation of the ITGB1-mediated cell adhesion and it's downstream signaling, thus indicating a potential novel role for GPRC5A in human epithelial cancers.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Integrin beta1
/
Receptors, G-Protein-Coupled
Limits:
Humans
Language:
En
Journal:
Cell Adh Migr
Year:
2017
Document type:
Article
Affiliation country:
Finlandia
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA