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Orphan G protein-coupled receptor GPRC5A modulates integrin ?1-mediated epithelial cell adhesion.


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 ?1 (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.

SUBMITTER: Bulanova DR 

PROVIDER: S-EPMC5810789 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Orphan G protein-coupled receptor GPRC5A modulates integrin β1-mediated epithelial cell adhesion.

Bulanova Daria R DR   Akimov Yevhen A YA   Rokka Anne A   Laajala Teemu D TD   Aittokallio Tero T   Kouvonen Petri P   Pellinen Teijo T   Kuznetsov Sergey G SG  

Cell adhesion & migration 20170206 5-6


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). Consi  ...[more]

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