Phosphatidic Acid Stimulates Lung Cancer Cell Migration through Interaction with the LPA1 Receptor and Subsequent Activation of MAP Kinases and STAT3
dc.contributor.author | Gómez Larrauri, Ana | |
dc.contributor.author | Gangoiti Muñecas, Patricia | |
dc.contributor.author | Camacho, Laura | |
dc.contributor.author | Presa Torre, Natalia | |
dc.contributor.author | Martín Plágaro, César Augusto | |
dc.contributor.author | Gómez Muñoz, Antonio | |
dc.date.accessioned | 2023-08-07T12:25:47Z | |
dc.date.available | 2023-08-07T12:25:47Z | |
dc.date.issued | 2023-06-23 | |
dc.identifier.citation | Biomedicines 11(7) : (2023) // Article ID 1804 | es_ES |
dc.identifier.issn | 2227-9059 | |
dc.identifier.uri | http://hdl.handle.net/10810/62124 | |
dc.description.abstract | Phosphatidic acid (PA) is a key bioactive glycerophospholipid that is implicated in the regulation of vital cell functions such as cell growth, differentiation, and migration, and is involved in a variety of pathologic processes. However, the molecular mechanisms by which PA exerts its pathophysiological actions are incompletely understood. In the present work, we demonstrate that PA stimulates the migration of the human non-small cell lung cancer (NSCLC) A549 adenocarcinoma cells, as determined by the transwell migration assay. PA induced the rapid phosphorylation of mitogen-activated protein kinases (MAPKs) ERK1-2, p38, and JNK, and the pretreatment of cells with selective inhibitors of these kinases blocked the PA-stimulated migration of cancer cells. In addition, the chemotactic effect of PA was inhibited by preincubating the cells with pertussis toxin (PTX), a Gi protein inhibitor, suggesting the implication of a Gi protein-coupled receptor in this action. Noteworthy, a blockade of LPA receptor 1 (LPA1) with the specific LPA1 antagonist AM966, or with the selective LPA1 inhibitors Ki1645 or VPC32193, abolished PA-stimulated cell migration. Moreover, PA stimulated the phosphorylation of the transcription factor STAT3 downstream of JAK2, and inhibitors of either JAK2 or STAT3 blocked PA-stimulated cell migration. It can be concluded that PA stimulates lung adenocarcinoma cell migration through an interaction with the LPA1 receptor and subsequent activation of the MAPKs ERK1-2, p38, and JNK, and that the JAK2/STAT3 pathway is also important in this process. These findings suggest that targeting PA formation and/or the LPA1 receptor may provide new strategies to reduce malignancy in lung cancer. | es_ES |
dc.description.sponsorship | This work was supported by Grant IT1720-22 from “Departamento de Educación, Viceconsejería de Universidades e Investigación del Gobierno Vasco” (GV/EJ, Basque Country, Spain). N. Presa is the recipient of a fellowship from “Departamento de Educación, Universidades e Investigación del Gobierno Vasco” (GV/EJ, Basque Country, Spain). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | phosphatidic acid | es_ES |
dc.subject | lysophosphatidic acid receptors | es_ES |
dc.subject | lung cancer cell migration | es_ES |
dc.subject | mitogen-activated protein kinases | es_ES |
dc.subject | Janus kinase | es_ES |
dc.subject | signal transducer and activator of transcription | es_ES |
dc.title | Phosphatidic Acid Stimulates Lung Cancer Cell Migration through Interaction with the LPA1 Receptor and Subsequent Activation of MAP Kinases and STAT3 | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2023-07-28T12:21:40Z | |
dc.rights.holder | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/2227-9059/11/7/1804 | es_ES |
dc.identifier.doi | 10.3390/biomedicines11071804 | |
dc.departamentoes | Bioquímica y biología molecular | |
dc.departamentoeu | Biokimika eta biologia molekularra |
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Except where otherwise noted, this item's license is described as © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).