RhoA/C inhibits proliferation by inducing the synthesis of GPRC5A

Abstract Rho GTPases are important regulators of many cellular functions like cell migration, adhesion and polarity. The molecular switches are often dysregulated in cancer. We detected Rho-dependent upregulation of the orphan seven-transmembrane receptor G-protein-coupled receptor family C group 5...

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Autores principales:	Lukas Richter, Viktoria Oberländer, Gudula Schmidt
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8f6413c594224f7bbb3b4cb4cb9557ea
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spelling	oai:doaj.org-article:8f6413c594224f7bbb3b4cb4cb9557ea2021-12-02T16:06:40ZRhoA/C inhibits proliferation by inducing the synthesis of GPRC5A10.1038/s41598-020-69481-22045-2322https://doaj.org/article/8f6413c594224f7bbb3b4cb4cb9557ea2020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-69481-2https://doaj.org/toc/2045-2322Abstract Rho GTPases are important regulators of many cellular functions like cell migration, adhesion and polarity. The molecular switches are often dysregulated in cancer. We detected Rho-dependent upregulation of the orphan seven-transmembrane receptor G-protein-coupled receptor family C group 5 member A (GPRC5A). GPRC5A is highly expressed in breast cancer whereas in lung cancer, it is often downregulated. Here, we analyzed the function of GPRC5A in breast epithelial and breast cancer cells. Activation or expression of RhoA/C led to GPRC5A-dependent inhibition of proliferation and reduction of the colony forming capacity of benign breast epithelial cells. This effect is based on an inhibition of EGFR signalling. Knockout of retinoic acid induced 3 (RAI3, the gene for GPRC5A) in breast cancer cells increased cell division, whereas Rho activation had no effect on proliferation. Knockout of RAI3 in benign breast epithelial cells led to decrease of EGFR expression and diminished proliferation.Lukas RichterViktoria OberländerGudula SchmidtNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lukas Richter Viktoria Oberländer Gudula Schmidt RhoA/C inhibits proliferation by inducing the synthesis of GPRC5A
description	Abstract Rho GTPases are important regulators of many cellular functions like cell migration, adhesion and polarity. The molecular switches are often dysregulated in cancer. We detected Rho-dependent upregulation of the orphan seven-transmembrane receptor G-protein-coupled receptor family C group 5 member A (GPRC5A). GPRC5A is highly expressed in breast cancer whereas in lung cancer, it is often downregulated. Here, we analyzed the function of GPRC5A in breast epithelial and breast cancer cells. Activation or expression of RhoA/C led to GPRC5A-dependent inhibition of proliferation and reduction of the colony forming capacity of benign breast epithelial cells. This effect is based on an inhibition of EGFR signalling. Knockout of retinoic acid induced 3 (RAI3, the gene for GPRC5A) in breast cancer cells increased cell division, whereas Rho activation had no effect on proliferation. Knockout of RAI3 in benign breast epithelial cells led to decrease of EGFR expression and diminished proliferation.
format	article
author	Lukas Richter Viktoria Oberländer Gudula Schmidt
author_facet	Lukas Richter Viktoria Oberländer Gudula Schmidt
author_sort	Lukas Richter
title	RhoA/C inhibits proliferation by inducing the synthesis of GPRC5A
title_short	RhoA/C inhibits proliferation by inducing the synthesis of GPRC5A
title_full	RhoA/C inhibits proliferation by inducing the synthesis of GPRC5A
title_fullStr	RhoA/C inhibits proliferation by inducing the synthesis of GPRC5A
title_full_unstemmed	RhoA/C inhibits proliferation by inducing the synthesis of GPRC5A
title_sort	rhoa/c inhibits proliferation by inducing the synthesis of gprc5a
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/8f6413c594224f7bbb3b4cb4cb9557ea
work_keys_str_mv	AT lukasrichter rhoacinhibitsproliferationbyinducingthesynthesisofgprc5a AT viktoriaoberlander rhoacinhibitsproliferationbyinducingthesynthesisofgprc5a AT gudulaschmidt rhoacinhibitsproliferationbyinducingthesynthesisofgprc5a
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RhoA/C inhibits proliferation by inducing the synthesis of GPRC5A

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