2026-06-02T21:36:20Zhttps://riuma.uma.es/rest/oai/requestoai:riuma.uma.es:10630/344302026-02-03T11:24:15Zcom_10630_2254col_10630_37953
RIUMA. Repositorio Institucional de la Universidad de Málaga
author
Jongsma, Maikel
author
Matas-Rico, Elisa
author
Jalink, Kees
author
Moolenaar, Wouter H
author
Rzadkowski, Adrian
2024-10-07T10:33:02Z
2024-10-07T10:33:02Z
2011-12
Jongsma M, Matas-Rico E, Rzadkowski A, Jalink K, Moolenaar WH (2011) LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor. PLoS ONE 6(12): e29260. https://doi.org/10.1371/journal.pone.0029260
https://hdl.handle.net/10630/34430
10.1371/journal.pone.0029260
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.
eng
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Melanoma
LPA is a chemorepellent for B16 melanoma cells: action through the cAMP-elevating LPA5 receptor
journal article
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URL
https://riuma.uma.es/bitstreams/b55f933a-e295-4e8a-b5b6-a037d976503e/download
File
MD5
3372bdb63331fd1e75bef8415dc702c1
1016761
application/pdf
PlusOne_2011.pdf