Nucleotide P2Y<sub>1</sub> receptor regulates EGF receptor mitogenic signaling and expression in epithelial cells

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dc.contributor.authorBuvinic, Sonja
dc.contributor.authorBravo-Zehnder, Marcela
dc.contributor.authorBoyer, Jose Luis
dc.contributor.authorHuidobro-Toro, Juan Pablo
dc.contributor.authorGonzalez, Alfonso
dc.date.accessioned2025-01-21T01:05:15Z
dc.date.available2025-01-21T01:05:15Z
dc.date.issued2007
dc.description.abstractEpidermal growth factor receptor ( EGFR) function is transregulated by a variety of stimuli, including agonists of certain G-protein-coupled receptors (GPCRs). One of the most ubiquitous GPCRs is the P2Y(1) receptor (P2RY1, hereafter referred to as P2Y(1)R) for extracellular nucleotides, mainly ADP. Here, we show in tumoral HeLa cells and normal FRT epithelial cells that P2Y(1)R broadcasts mitogenic signals by transactivating the EGFR. The pathway involves PKC, Src and cell surface metalloproteases. Stimulation of P2Y(1)R for as little as 1560 minutes triggers mitogenesis, mirroring the half-life of extracellular ADP. Apyrase degradation of extracellular nucleotides and drug inhibition of P2Y(1)R, both reduced basal cell proliferation of HeLa and FRT cells, but not MDCK cells, which do not express P2Y(1)R. Thus, cell-released nucleotides constitute strong mitogenic stimuli, which act via P2Y(1)R. Strikingly, MDCK cells ectopically expressing P2Y(1)R display a highly proliferative phenotype that depends on EGFR activity associated with an increased level of EGFR, thus disclosing a novel aspect of GPCR-mediated regulation of EGFR function. These results highlight a role of P2Y(1)R in EGFR-dependent epithelial cell proliferation. P2Y(1)R could potentially mediate both trophic stimuli of basally released nucleotides and first-line mitogenic stimulation upon tissue damage. It could also contribute to carcinogenesis and serve as target for antitumor therapies.
dc.fuente.origenWOS
dc.identifier.doi10.1242/jcs.03490
dc.identifier.eissn1477-9137
dc.identifier.issn0021-9533
dc.identifier.urihttps://doi.org/10.1242/jcs.03490
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95874
dc.identifier.wosidWOS:000252243300007
dc.issue.numero24
dc.language.isoen
dc.pagina.final4301
dc.pagina.inicio4289
dc.revistaJournal of cell science
dc.rightsacceso restringido
dc.subjectnucleotides
dc.subjectGPCR
dc.subjectEGFR
dc.subjecttransactivation
dc.subjectepithelia
dc.subjectproliferation
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleNucleotide P2Y<sub>1</sub> receptor regulates EGF receptor mitogenic signaling and expression in epithelial cells
dc.typeartículo
dc.volumen120
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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