Anti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/Ca2+/ß-catenin Pathway.
Sci Rep
; 7(1): 2459, 2017 05 26.
Article
en En
| MEDLINE
| ID: mdl-28550303
ABSTRACT
Although purinegic signaling is important in regulating gastric physiological functions, it is currently unknown for its role in gastric cancer (GC). We demonstrate for the first time that the expression of P2Y6 receptors was markedly down-regulated in human GC cells and primary GC tissues compared to normal tissues, while the expression of P2Y2 and P2Y4 receptors was up-regulated in GC cells. Moreover, the expression levels of P2Y6 receptors in GC tissues were correlated to tumor size, differentiation, metastasis to lymph nodes, and the survival rate of the patients with GC. Ncleotides activated P2Y6 receptors to raise cytosolic Ca2+ concentrations in GC cells through store-operated calcium entry (SOCE), and then mediated Ca2+-dependent inhibition of ß-catenin and proliferation, eventually leading to GC suppression. Furthermore, UTP particularly blocked the G1/S transition of GC cells but did not induce apoptosis. Collectively, we conclude that nucleotides activate P2Y6 receptors to suppress GC growth through a novel SOCE/Ca2+/ß-catenin-mediated anti-proliferation of GC cells, which is different from the canonical SOCE/Ca2+-induced apoptosis in other tumors.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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Uridina Trifosfato
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Canales de Calcio
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Regulación Neoplásica de la Expresión Génica
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Receptores Purinérgicos P2
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Beta Catenina
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Antineoplásicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Sci Rep
Año:
2017
Tipo del documento:
Article