Extracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells

Extracellular ATP in the tumor microenvironment exhibits either pro- or antitumor effect via interaction with P2Y receptors, but the intracellular signaling and functional roles of P2Y receptors in oral squamous cell carcinoma (OSCC) are unclear. We aimed to study the effect of ATP on OSCC cell line...

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Autores principales:	Chia Chih Lau, Amnani Aminuddin, Kok Meng Chan, Ian C. Paterson, Lok Mun Law, Pei Yuen Ng
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	extracellular ATP oral squamous cell carcinoma P2Y receptors ERK signaling S-phase arrest Science Q
Acceso en línea:	https://doaj.org/article/ff61f319a17142b095effa1ebf562787
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spelling	oai:doaj.org-article:ff61f319a17142b095effa1ebf5627872021-11-25T18:10:52ZExtracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells10.3390/life111111702075-1729https://doaj.org/article/ff61f319a17142b095effa1ebf5627872021-11-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1170https://doaj.org/toc/2075-1729Extracellular ATP in the tumor microenvironment exhibits either pro- or antitumor effect via interaction with P2Y receptors, but the intracellular signaling and functional roles of P2Y receptors in oral squamous cell carcinoma (OSCC) are unclear. We aimed to study the effect of ATP on OSCC cell lines and the potential mechanisms involved. Through GEPIA dataset analysis, high expression levels of mRNA encoding P2Y receptors, the ATP-induced G protein-coupled receptors, were associated with better overall patient survival in head and neck squamous cell carcinoma. qPCR analysis showed that the poorly differentiated OSCC SAS cell line, had higher <i>P2RY1</i> expression level compared to the well-differentiated H103 and H376 cell lines. Western blotting and flow cytometry analyses revealed that ATP phosphorylated ERK and elevated intracellular calcium signaling in all tested cell lines. A significant S-phase cell cycle arrest was observed in SAS, and preincubation with the MEK inhibitor PD0325901 reversed the ATP-induced S-phase arrest. We further demonstrated that ATP induced a slight reduction in cell count and colony formation yet significant apoptosis in SAS. Overall, we postulate that the ATP-induced S-phase arrest effect in SAS cells may be regulated through P2Y receptor-mediated ERK signaling, thus suggesting a potential antitumor effect of ATP via interaction with its distinct profile of P2Y receptors.Chia Chih LauAmnani AminuddinKok Meng ChanIan C. PatersonLok Mun LawPei Yuen NgMDPI AGarticleextracellular ATPoral squamous cell carcinomaP2Y receptorsERK signalingS-phase arrestScienceQENLife, Vol 11, Iss 1170, p 1170 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	extracellular ATP oral squamous cell carcinoma P2Y receptors ERK signaling S-phase arrest Science Q
spellingShingle	extracellular ATP oral squamous cell carcinoma P2Y receptors ERK signaling S-phase arrest Science Q Chia Chih Lau Amnani Aminuddin Kok Meng Chan Ian C. Paterson Lok Mun Law Pei Yuen Ng Extracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells
description	Extracellular ATP in the tumor microenvironment exhibits either pro- or antitumor effect via interaction with P2Y receptors, but the intracellular signaling and functional roles of P2Y receptors in oral squamous cell carcinoma (OSCC) are unclear. We aimed to study the effect of ATP on OSCC cell lines and the potential mechanisms involved. Through GEPIA dataset analysis, high expression levels of mRNA encoding P2Y receptors, the ATP-induced G protein-coupled receptors, were associated with better overall patient survival in head and neck squamous cell carcinoma. qPCR analysis showed that the poorly differentiated OSCC SAS cell line, had higher <i>P2RY1</i> expression level compared to the well-differentiated H103 and H376 cell lines. Western blotting and flow cytometry analyses revealed that ATP phosphorylated ERK and elevated intracellular calcium signaling in all tested cell lines. A significant S-phase cell cycle arrest was observed in SAS, and preincubation with the MEK inhibitor PD0325901 reversed the ATP-induced S-phase arrest. We further demonstrated that ATP induced a slight reduction in cell count and colony formation yet significant apoptosis in SAS. Overall, we postulate that the ATP-induced S-phase arrest effect in SAS cells may be regulated through P2Y receptor-mediated ERK signaling, thus suggesting a potential antitumor effect of ATP via interaction with its distinct profile of P2Y receptors.
format	article
author	Chia Chih Lau Amnani Aminuddin Kok Meng Chan Ian C. Paterson Lok Mun Law Pei Yuen Ng
author_facet	Chia Chih Lau Amnani Aminuddin Kok Meng Chan Ian C. Paterson Lok Mun Law Pei Yuen Ng
author_sort	Chia Chih Lau
title	Extracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells
title_short	Extracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells
title_full	Extracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells
title_fullStr	Extracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells
title_full_unstemmed	Extracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells
title_sort	extracellular atp induced s-phase cell cycle arrest via p2y receptor-activated erk signaling in poorly differentiated oral squamous cell carcinoma sas cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ff61f319a17142b095effa1ebf562787
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Extracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells

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