LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor

Lysophosphatidic acid (LPA), a lipid mediator enriched in serum, stimulates cell migration, proliferation and other functions in many cell types. LPA acts on six known G protein-coupled receptors, termed LPA1–6, showing both overlapping and distinct signaling properties. Here we show that, unexpecte...

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Main Authors:	Jongsma, Maikel, Matas-Rico, Elisa, Rzadkowski, Adrian, Jalink, Kees, Moolenaar, Wouter H.
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237609/

id	pubmed-3237609
recordtype	oai_dc
spelling	pubmed-32376092011-12-22 LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor Jongsma, Maikel Matas-Rico, Elisa Rzadkowski, Adrian Jalink, Kees Moolenaar, Wouter H. Research Article Lysophosphatidic acid (LPA), a lipid mediator enriched in serum, stimulates cell migration, proliferation and other functions in many cell types. LPA acts on six known G protein-coupled receptors, termed LPA1–6, showing both overlapping and distinct signaling properties. Here we show that, unexpectedly, LPA and serum almost completely inhibit the transwell migration of B16 melanoma cells, with alkyl-LPA(18∶1) being 10-fold more potent than acyl-LPA(18∶1). The anti-migratory response to LPA is highly polarized and dependent on protein kinase A (PKA) but not Rho kinase activity; it is associated with a rapid increase in intracellular cAMP levels and PIP3 depletion from the plasma membrane. B16 cells express LPA2, LPA5 and LPA6 receptors. We show that LPA-induced chemorepulsion is mediated specifically by the alkyl-LPA-preferring LPA5 receptor (GPR92), which raises intracellular cAMP via a noncanonical pathway. Our results define LPA5 as an anti-migratory receptor and they implicate the cAMP-PKA pathway, along with reduced PIP3 signaling, as an effector of chemorepulsion in B16 melanoma cells. Public Library of Science 2011-12-14 /pmc/articles/PMC3237609/ /pubmed/22195035 http://dx.doi.org/10.1371/journal.pone.0029260 Text en Jongsma et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Jongsma, Maikel Matas-Rico, Elisa Rzadkowski, Adrian Jalink, Kees Moolenaar, Wouter H.
spellingShingle	Jongsma, Maikel Matas-Rico, Elisa Rzadkowski, Adrian Jalink, Kees Moolenaar, Wouter H. LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor
author_facet	Jongsma, Maikel Matas-Rico, Elisa Rzadkowski, Adrian Jalink, Kees Moolenaar, Wouter H.
author_sort	Jongsma, Maikel
title	LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor
title_short	LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor
title_full	LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor
title_fullStr	LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor
title_full_unstemmed	LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor
title_sort	lpa is a chemorepellent for b16 melanoma cells: action through the camp-elevating lpa5 receptor
description	Lysophosphatidic acid (LPA), a lipid mediator enriched in serum, stimulates cell migration, proliferation and other functions in many cell types. LPA acts on six known G protein-coupled receptors, termed LPA1–6, showing both overlapping and distinct signaling properties. Here we show that, unexpectedly, LPA and serum almost completely inhibit the transwell migration of B16 melanoma cells, with alkyl-LPA(18∶1) being 10-fold more potent than acyl-LPA(18∶1). The anti-migratory response to LPA is highly polarized and dependent on protein kinase A (PKA) but not Rho kinase activity; it is associated with a rapid increase in intracellular cAMP levels and PIP3 depletion from the plasma membrane. B16 cells express LPA2, LPA5 and LPA6 receptors. We show that LPA-induced chemorepulsion is mediated specifically by the alkyl-LPA-preferring LPA5 receptor (GPR92), which raises intracellular cAMP via a noncanonical pathway. Our results define LPA5 as an anti-migratory receptor and they implicate the cAMP-PKA pathway, along with reduced PIP3 signaling, as an effector of chemorepulsion in B16 melanoma cells.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237609/
_version_	1611493993862922240

LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor

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