Extracellular ATP/P2X7 receptor, a regulatory axis of migration in ovarian carcinomaderived cells


Por: Nuñez-Ríos J.D., Reyna-Jeldes M., Mata-Martínez E., del Rocío Campos-Contreras A., Lazcano-Sánchez I., González-Gallardo A., Díaz-Muñoz M., Coddou C., Vázquez-Cuevas F.G.

Publicada: 1 ene 2024
Resumen:
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 receptor is a regulator for cancer cell migration and thus a potential drug target. © 2024 Nuñez-Ríos 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.

Filiaciones:
Nuñez-Ríos J.D.:
 Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico

Reyna-Jeldes M.:
 Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo, Chile

 Millennium Nucleus for the Study of Pain (MiNuSPain), Santiago, Chile

 Núcleo Para el Estudio del Cáncer a Nivel Básico Aplicado y Clínico, Universidad Católica del Norte, Coquimbo, Chile

Mata-Martínez E.:
 Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico

del Rocío Campos-Contreras A.:
 Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico

Lazcano-Sánchez I.:
 Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico

González-Gallardo A.:
 Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico

Díaz-Muñoz M.:
 Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico

Coddou C.:
 Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo, Chile

 Millennium Nucleus for the Study of Pain (MiNuSPain), Santiago, Chile

 Núcleo Para el Estudio del Cáncer a Nivel Básico Aplicado y Clínico, Universidad Católica del Norte, Coquimbo, Chile

Vázquez-Cuevas F.G.:
 Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico
ISSN: 19326203
Editorial
PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 19 Número: 6
Páginas:
WOS Id: 001248345600087
ID de PubMed: 38870128
imagen Green Accepted, gold, All Open Access; Gold Open Access

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