Extracellular ATP/P2X7 receptor, a regulatory axis of migration in ovarian carcinoma-derived cells
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View abstract on PubMed
Summary
This summary is machine-generated.Extracellular ATP fuels cancer progression via P2X7 receptors. Depleting ATP or blocking P2X7 inhibits ovarian cancer cell migration and mesenchymal phenotype, identifying P2X7 as a potential drug target.
Area Of Science
- Oncology
- Molecular Biology
- Cell Biology
Background
- High extracellular ATP concentrations in cancer promote malignant phenotypes via P2 receptors.
- The P2X7 receptor (P2RX7) is implicated in cancer progression.
Purpose Of The Study
- To investigate the role of extracellular ATP and the P2X7 receptor in ovarian cancer cell migration and phenotype.
- To evaluate P2X7 as a potential therapeutic target in ovarian carcinoma.
Main Methods
- Utilized SKOV-3 (metastatic ovarian carcinoma) and HOSE6-3 (healthy ovarian surface epithelium) cell lines.
- Employed extracellular ATP depletion with apyrase, pharmacological P2X7 activation/antagonism (BzATP, A438079, BBG, OxATP), transcript analysis, bioinformatic analysis, and CRISPR-based P2RX7 knockout.
- Assessed cell migration (wound-healing assay), transepithelial electrical resistance, cell markers, E-cadherin expression, and calcium mobilization.
Main Results
- Extracellular ATP depletion reduced SKOV-3 cell migration and mesenchymal phenotype markers.
- P2RX7 transcript levels were significantly higher in SKOV-3 cells and metastatic tissues compared to healthy cells and primary tumors, respectively.
- P2X7 activation promoted cell migration and decreased E-cadherin expression, while P2X7 antagonists and P2RX7 knockout reduced migration and calcium mobilization.
Conclusions
- The P2X7 receptor plays a crucial role in regulating ovarian cancer cell migration and maintaining a mesenchymal phenotype.
- P2X7 is a promising therapeutic target for inhibiting cancer progression in ovarian carcinoma.
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