التفاصيل البيبلوغرافية
العنوان: |
Extracellular ATP/P2X7 receptor, a regulatory axis of migration in ovarian carcinoma-derived cells. |
المؤلفون: |
Nuñez-Ríos, José David, Reyna-Jeldes, Mauricio, Mata-Martínez, Esperanza, Campos-Contreras, Anaí del Rocío, Lazcano-Sánchez, Iván, González-Gallardo, Adriana, Díaz-Muñoz, Mauricio, Coddou, Claudio, Vázquez-Cuevas, Francisco G. |
المصدر: |
PLoS ONE; 6/13/2024, Vol. 19 Issue 6, p1-24, 24p |
مصطلحات موضوعية: |
PURINERGIC receptors, CANCER cell migration, CELL migration, CELL receptors, DRUG target, PHENOTYPES |
مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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قاعدة البيانات: |
Complementary Index |