Anti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/Ca2+/β-catenin Pathway

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...

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Autores principales:	Hanxing Wan, Rui Xie, Jiangyu Xu, Jialin He, Bo Tang, Qingqing Liu, Sumin Wang, Yanjun Guo, Xin Yang, Tobias Xiao Dong, John M. Carethers, Shiming Yang, Hui Dong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69858d18ef004a059ef1b932cb5acecf
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spelling	oai:doaj.org-article:69858d18ef004a059ef1b932cb5acecf2021-12-02T15:05:00ZAnti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/Ca2+/β-catenin Pathway10.1038/s41598-017-02562-x2045-2322https://doaj.org/article/69858d18ef004a059ef1b932cb5acecf2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02562-xhttps://doaj.org/toc/2045-2322Abstract 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 β-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+/β-catenin-mediated anti-proliferation of GC cells, which is different from the canonical SOCE/Ca2+-induced apoptosis in other tumors.Hanxing WanRui XieJiangyu XuJialin HeBo TangQingqing LiuSumin WangYanjun GuoXin YangTobias Xiao DongJohn M. CarethersShiming YangHui DongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hanxing Wan Rui Xie Jiangyu Xu Jialin He Bo Tang Qingqing Liu Sumin Wang Yanjun Guo Xin Yang Tobias Xiao Dong John M. Carethers Shiming Yang Hui Dong Anti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/Ca2+/β-catenin Pathway
description	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 β-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+/β-catenin-mediated anti-proliferation of GC cells, which is different from the canonical SOCE/Ca2+-induced apoptosis in other tumors.
format	article
author	Hanxing Wan Rui Xie Jiangyu Xu Jialin He Bo Tang Qingqing Liu Sumin Wang Yanjun Guo Xin Yang Tobias Xiao Dong John M. Carethers Shiming Yang Hui Dong
author_facet	Hanxing Wan Rui Xie Jiangyu Xu Jialin He Bo Tang Qingqing Liu Sumin Wang Yanjun Guo Xin Yang Tobias Xiao Dong John M. Carethers Shiming Yang Hui Dong
author_sort	Hanxing Wan
title	Anti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/Ca2+/β-catenin Pathway
title_short	Anti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/Ca2+/β-catenin Pathway
title_full	Anti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/Ca2+/β-catenin Pathway
title_fullStr	Anti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/Ca2+/β-catenin Pathway
title_full_unstemmed	Anti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/Ca2+/β-catenin Pathway
title_sort	anti-proliferative effects of nucleotides on gastric cancer via a novel p2y6/soce/ca2+/β-catenin pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/69858d18ef004a059ef1b932cb5acecf
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Anti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/Ca2+/β-catenin Pathway

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