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

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Bulanova , D R , Akimov , Y A , Rokka , A , Laajala , T D , Aittokallio , T , Kouvonen , P , Pellinen , T & Kuznetsov , S G 2017 , ' Orphan G protein-coupled receptor GPRC5A modulates integrin beta 1-mediated epithelial cell adhesion ' , Cell Adhesion & Migration , vol. 11 , no. 5-6 , pp. 434-446 . https://doi.org/10.1080/19336918.2016.1245264

Title: Orphan G protein-coupled receptor GPRC5A modulates integrin beta 1-mediated epithelial cell adhesion
Author: Bulanova, Daria R.; Akimov, Yevhen A.; Rokka, Anne; Laajala, Teemu D.; Aittokallio, Tero; Kouvonen, Petri; Pellinen, Teijo; Kuznetsov, Sergey G.
Other contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland





Date: 2017
Language: eng
Number of pages: 13
Belongs to series: Cell Adhesion & Migration
ISSN: 1933-6918
DOI: https://doi.org/10.1080/19336918.2016.1245264
URI: http://hdl.handle.net/10138/232155
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 beta 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.
Subject: ECM
EphA2
GPRC5A
integrin beta 1
matrix adhesion
TUMOR-SUPPRESSOR GPRC5A
SRC FAMILY KINASES
RETINOIC ACID
TYROSINE PHOSPHORYLATION
EXTRACELLULAR-MATRIX
FOCAL ADHESIONS
BREAST-CANCER
LUNG-CANCER
IN-VIVO
ACTIVATION
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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