Extracellular ATP/P2X7 receptor - a regulatory axis of migration in ovarian carcinoma-derived cells

Sep 21, 2026

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ATP is actively maintained at high concentrations in cancerous tissues, where it promotes a malignant phenotype through P2 receptors. This study evaluates extracellular ATP depletion with apyrase in SKOV-3 ovarian carcinoma cells, observing reduced migration, increased transepithelial electrical resistance, and shifts toward a mesenchymal phenotype. Transcript comparisons identify P2RX7 as markedly higher in SKOV-3 than in HOSE6-3, with higher expression in metastatic tissues. Functional experiments show P2X7 promotes migration, increases E-cadherin loss via BzATP, while multiple P2X7 antagonists reduce migration and CRISPR knockout impairs receptor-linked calcium mobilization and migration.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages24

Reading Time1 h 0 min

AccessFree to download

Abstract

Introduction

Ovarian cancer lethality and metastasis mechanisms

EMT-driven migration in ovarian carcinoma

Materials and methods

ATP depletion and migration assays

P2 receptor expression analysis and bioinformatics

Pharmacological modulation and CRISPR-based knockout

Results

P2X7 regulates migration and mesenchymal phenotype

BzATP effects and antagonist inhibition

P2RX7 knockout effects on calcium mobilization and migration

Discussion

P2X7 as a potential drug target

PLOS ONE OPEN ACCESS Citation: Nuñez-R´ıos JD, Reyna-Jeldes M, MataMart´ınez E, Campos-Contreras AdR, LazcanoS´anchez I, Gonz´alez-Gallardo A, et al. (2024) Extracellular ATP/P2X7 receptor, a regulatory axis of migration in ovarian carcinoma-derived cells. PLoS ONE 19(6): e0304062 . [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1371/journal.pone](10.1371/journal.pone).0304062 Editor: Altaf Mohammed, National Cancer Institute, UNITED STATES Received: January 23, 2024 Accepted: May 6, 2024 Published: June 13, 2024 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: [https://doi.org/10.1371/journal.pone.0304062](https://doi.org/10.1371/journal.pone.0304062) [Copyright:](Copyright:) © [2024](2024) Nuñez-R´ıos et al. 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 credited. Data Availability Statement: Microarray data were deposited by pur group in ArrayExpress. Accesion number:E-MTAB-13598. All other relevant data are RESEARCH ARTICLE Extracellular ATP/P2X7 receptor, a regulatory axis of migration in ovarian carcinomaderived cells Jos´e David Nuñez-R´ıos1, Mauricio Reyna-Jeldes2,3,4, Esperanza Mata-Mart´ınez1, Ana´ı del Roc´ıo Campos-Contreras1¤, Iv´an Lazcano-S´anchez1, Adriana Gonz´alez-Gallardo1, Mauricio D´ıaz-Muñoz1, Claudio Coddou2,3,4, Francisco G. V´azquez-Cuevas1 * 1 Departamento de Neurobiolog´ıa Celular y Molecular, Instituto de Neurobiolog´ıa, Universidad Nacional Aut´onomade M´exico, Quer´etaro, M´exico, 2 Departamento de Ciencias Biom´edicas, Facultad de Medicina, Universidad Cat´olica del Norte, Coquimbo, Chile, 3 Millennium Nucleus for the Study of Pain (MiNuSPain), Santiago, Chile, 4 N´ucleo Para el Estudio del C´ancer a Nivel B´asico, Aplicado y Cl´ınico, Universidad Cat´olicadel Norte, Coquimbo, Chile ¤ Current address: Facultad de Ingenier´ıa, Universidad Aut´onomade Quer´etaro, Quer´etaro, M´exico * [fvazquez@comunidad.unam.mx](fvazquez@comunidad.unam.mx) Abstract ATP is actively maintained at high concentrations in cancerous tissues, where it promotes a malignant phenotype through P2 receptors. In this study, we first evaluated the effect of extracellular ATP depletion with apyrase in SKOV-3, a cell line derived from metastatic ovarian carcinoma. We observed a decrease in cell migration and an increase in transepithelial electrical resistance and cell markers, suggesting a role in maintaining a mesenchymal phenotype. To identify the P2 receptor that mediated the effects of ATP, we compared the transcript levels of some P2 receptors and found that P2RX7 is three-fold higher in SKOV-3 cells than in a healthy cell line, namely HOSE6-3 (from human ovarian surface epithelium) . Through bioinformatic analysis, we identified a higher expression of the P2RX7 transcript in metastatic tissues than in primary tumors; thus, P2X7 seems to be a promising effector for the malignant phenotype. Subsequently, we demonstrated the presence and functionality of the P2X7 receptor in SKOV-3 cells and showed through pharmacological approaches that its activity promotes cell migration and contributes to maintaining a mesenchymal phenotype. P2X7 activation using BzATP increased cell migration and abolished E-cadherin expression. On the other hand, a series of P2X7 receptor antagonists (A438079, BBG and OxATP) decreased cell migration. We used a CRISPR-based knock-out system directed to P2RX7. According to the results of our wound-healing assay, SKOV3-P2X7KO cells lacked receptor-mediated calcium mobilization and decreased migration. Altogether, these data let us propose that P2X7 rec

FAQs

How does extracellular ATP affect migration in SKOV-3 ovarian carcinoma-derived cells?

Extracellular ATP depletion with apyrase decreases cell migration, along with increased transepithelial electrical resistance and changes in cell markers consistent with maintaining a mesenchymal phenotype.

Which P2 receptor is implicated as the mediator of ATP’s effects and what evidence supports it?

P2RX7. Transcript comparisons show P2RX7 is about three-fold higher in SKOV-3 than in the healthy HOSE6-3 line, and bioinformatic analysis indicates higher P2RX7 transcript expression in metastatic tissues than in primary tumors.

What experimental approaches demonstrate that P2X7 promotes migration?

BzATP activation increases cell migration and abolishes E-cadherin expression, while P2X7 antagonists (A438079, BBG, OxATP) decrease migration. CRISPR-based P2RX7 knockout also reduces receptor-mediated calcium mobilization and lowers migration in a wound-healing assay.

Sep 21, 2026

Uploaded by Violet