Purinergic signaling, mediated by extracellular nucleotides such as ATP and UTP, has been increasingly studied for its role in regulating cellular communication. A new review by researchers in Singapore examines the P2Y2 receptor, a G protein–coupled receptor activated by these nucleotides, and summarizes current evidence regarding its functions in cancer.
The authors reported that P2Y2 signaling has been associated with multiple cancer-related processes, including cell proliferation, migration, and epithelial–mesenchymal transition (EMT), based on findings from previously published studies. In addition, the receptor has been linked to intracellular signaling pathways such as EGFR, PI3K–AKT, and MAPK, which are known to regulate cell growth and survival.
The review also highlights the potential role of P2Y2 in the tumor microenvironment. Extracellular ATP, which can be released by tumor and stromal cells, may activate purinergic receptors and influence processes such as inflammation, angiogenesis, and immune responses. These effects are context-dependent and may vary across tumor types and experimental conditions.
Furthermore, the review discusses the possibility that P2Y2 could serve as a biomarker, as its expression has been reported to correlate with disease progression or prognosis in certain cancers in bioinformatic and experimental studies. However, further validation is needed.
The authors also review current strategies for targeting P2Y2, including pharmacological modulation and gene-based approaches. While compounds targeting purinergic receptors have been developed in other clinical contexts, the application of P2Y2-targeted therapies in oncology remains under investigation.
Overall, the review consolidates existing knowledge and identifies areas for future research, particularly regarding the context-specific roles of P2Y2 signaling and its potential clinical relevance.
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Contact the author: Wanjin Hong (hong_wanjin@a-star.edu.sg) and Gandhi T. K. Boopathy (gandhibtk@a-star.edu.sg), Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore.
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Systematic review
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P2Y2 signaling in cancer: mechanisms, biomarkers, and therapeutic horizons
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Wanjin Hong is the Co-Editor-in-Chief of Molecular and Digital Medicine and was not involved in the editorial review or the decision to publish this article.