ArticleFrontiers in pharmacology2020
Extracellular ATP Mediates Cancer Cell Migration and Invasion Through Increased Expression of Cyclooxygenase 2.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- ATP is not always pro-inflammatory: rethinking purinergic signalling in cancer and autoimmunity.Purinergic signalling · 2026Review
- A genome-wide genetic screen reveals the P2Y2-integrin axis as a stabilizer of EGFR mutants in non-small cell lung cancer (NSCLC).Science advances · 2026Article
- Ecto-5'-nucleotidase/CD73 reduces COX-2 expression in activated macrophages.Scientific reports · 2026Article
- ATP-Powered Signaling Between Artificial and Living Cells.Angewandte Chemie (International ed. in English) · 2025Article
- Platelet-derived microvesicles modulate the bioenergetic and inflammatory phenotype of human polymorphonuclear leukocytes.Journal of leukocyte biology · 2025Article
- Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.Purinergic signalling · 2025Review
- Role of the P2X7 receptor in breast cancer progression.Purinergic signalling · 2025Review
- Role and recent progress of P2Y12 receptor in cancer development.Purinergic signalling · 2025Review
- P2Y12 receptor-mediated cyclooxygenase 2 (COX-2) expression enhances tumor cell progression in a mouse model of lymphoma.Purinergic signalling · 2025Article
- Mechanical Modulation, Physiological Roles, and Imaging Innovations of Intercellular Calcium Waves in Living Systems.Cancers · 2025Review
- Significance of non-steroidal anti-inflammatory drugs in the prevention and treatment of cervical cancer.Heliyon · 2025Review
- ATP released by ultrasound targeted microbubble cavitation induces vascular inflammation and improves immune checkpoint blockade efficacy.Theranostics · 2025Article
- Role of P2X7 receptor in the progression and clinicopathological characteristics of gastric cancer.Scientific reports · 2024Article
- Article
- Extracellular ATP/P2X7 receptor, a regulatory axis of migration in ovarian carcinoma-derived cells.PloS one · 2024Article
- P2X7 receptor promotes migration and invasion of non-small cell lung cancer A549 cells through the PI3K/Akt pathways.Purinergic signalling · 2023Article
- Purine and purinergic receptors in health and disease.MedComm · 2023Review
- Human soluble CD39 displays substrate inhibition in a substrate-specific manner.Scientific reports · 2023Article
- The circadian regulation of extracellular ATP.Purinergic signalling · 2023Review
- An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential.Cancer cell international · 2023Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor microenvironment plays a major role in the ability of the tumor cells to undergo metastasis. A major player of tumors gaining metastatic property is the inflammatory protein, cyclooxygenase 2 (COX-2). Several tumors show upregulation of this protein, which has been implicated in mediating metastasis in various cancer types such as of colon, breast and lung. In this report, we show that the concentration of extracellular ATP (eATP) is increased in response to cell death mediated by chemotherapeutic agents such as doxorubicin. By using three different cell-lines-HeLa (cervical), IMR-32 (neuronal) and MCF-7 (breast)-we show that this eATP goes on to act on purinergic (P2) receptors. Among the various P2 receptors expressed in these cells we identified P2X7, in IMR-32 and MCF-7 cells, and P2Y12, in HeLa cells, as important in modulating cell migration and invasion. Downstream of the P2 receptor activation, both p42/44 mitogen-activated protein kinase (MAPK) and the p38 MAPK are activated in these cells. These result in an increase in the expression of COX-2 mRNA and protein. We also observe an increase in the activity of matrix metalloproteinase 2 (MMP-2) enzyme in these cells. Blocking the P2 receptors not only blocks migration and invasion, but also COX-2 synthesis and MMP-2 activity. Our results show the link between purinergic receptors and COX-2 expression. Increased levels of ATP in the tumor microenvironment, therefore, leads to increased COX-2 expression, which, in turn, affords migratory and invasive properties to the tumor. This provides P2 receptor-based anti-inflammatory drugs (PBAIDs) a potential opportunity to be explored as cancer therapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.