Role of Orai3 in the Pathophysiology of Cancer

The mammalian exclusive Orai3 channel participates in the generation and/or modulation of two independent Ca<sup>2+</sup> currents, the store-operated current, I<sub>crac</sub>, involving functional interactions between the stromal interaction molecules (STIM), STIM1/STIM2, a...

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Autores principales:	Jose Sanchez-Collado, Isaac Jardin, Jose J. López, Victor Ronco, Gines M. Salido, Charlotte Dubois, Natalia Prevarskaya, Juan A. Rosado
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	orai3 orai1 calcium entry cancer Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/00de6fa110e14c78983b91618feee454
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spelling	oai:doaj.org-article:00de6fa110e14c78983b91618feee4542021-11-11T16:53:48ZRole of Orai3 in the Pathophysiology of Cancer10.3390/ijms2221114261422-00671661-6596https://doaj.org/article/00de6fa110e14c78983b91618feee4542021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11426https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The mammalian exclusive Orai3 channel participates in the generation and/or modulation of two independent Ca<sup>2+</sup> currents, the store-operated current, I<sub>crac</sub>, involving functional interactions between the stromal interaction molecules (STIM), STIM1/STIM2, and Orai1/Orai2/Orai3, as well as the store-independent arachidonic acid (AA) (or leukotriene C4)-regulated current I<sub>a</sub><sub>rc</sub>, which involves Orai1, Orai3 and STIM1. Overexpression of functional Orai3 has been described in different neoplastic cells and cancer tissue samples as compared to non-tumor cells or normal adjacent tissue. In these cells, Orai3 exhibits a cell-specific relevance in Ca<sup>2+</sup> influx. In estrogen receptor-positive breast cancer cells and non-small cell lung cancer (NSCLC) cells store-operated Ca<sup>2+</sup> entry (SOCE) is strongly dependent on Orai3 expression while in colorectal cancer and pancreatic adenocarcinoma cells Orai3 predominantly modulates SOCE. On the other hand, in prostate cancer cells Orai3 expression has been associated with the formation of Orai1/Orai3 heteromeric channels regulated by AA and reduction in SOCE, thus leading to enhanced proliferation. Orai3 overexpression is associated with supporting several cancer hallmarks, including cell cycle progression, proliferation, migration, and apoptosis resistance. This review summarizes the current knowledge concerning the functional role of Orai3 in the pathogenesis of cancer.Jose Sanchez-ColladoIsaac JardinJose J. LópezVictor RoncoGines M. SalidoCharlotte DuboisNatalia PrevarskayaJuan A. RosadoMDPI AGarticleorai3orai1calcium entrycancerBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11426, p 11426 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	orai3 orai1 calcium entry cancer Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	orai3 orai1 calcium entry cancer Biology (General) QH301-705.5 Chemistry QD1-999 Jose Sanchez-Collado Isaac Jardin Jose J. López Victor Ronco Gines M. Salido Charlotte Dubois Natalia Prevarskaya Juan A. Rosado Role of Orai3 in the Pathophysiology of Cancer
description	The mammalian exclusive Orai3 channel participates in the generation and/or modulation of two independent Ca<sup>2+</sup> currents, the store-operated current, I<sub>crac</sub>, involving functional interactions between the stromal interaction molecules (STIM), STIM1/STIM2, and Orai1/Orai2/Orai3, as well as the store-independent arachidonic acid (AA) (or leukotriene C4)-regulated current I<sub>a</sub><sub>rc</sub>, which involves Orai1, Orai3 and STIM1. Overexpression of functional Orai3 has been described in different neoplastic cells and cancer tissue samples as compared to non-tumor cells or normal adjacent tissue. In these cells, Orai3 exhibits a cell-specific relevance in Ca<sup>2+</sup> influx. In estrogen receptor-positive breast cancer cells and non-small cell lung cancer (NSCLC) cells store-operated Ca<sup>2+</sup> entry (SOCE) is strongly dependent on Orai3 expression while in colorectal cancer and pancreatic adenocarcinoma cells Orai3 predominantly modulates SOCE. On the other hand, in prostate cancer cells Orai3 expression has been associated with the formation of Orai1/Orai3 heteromeric channels regulated by AA and reduction in SOCE, thus leading to enhanced proliferation. Orai3 overexpression is associated with supporting several cancer hallmarks, including cell cycle progression, proliferation, migration, and apoptosis resistance. This review summarizes the current knowledge concerning the functional role of Orai3 in the pathogenesis of cancer.
format	article
author	Jose Sanchez-Collado Isaac Jardin Jose J. López Victor Ronco Gines M. Salido Charlotte Dubois Natalia Prevarskaya Juan A. Rosado
author_facet	Jose Sanchez-Collado Isaac Jardin Jose J. López Victor Ronco Gines M. Salido Charlotte Dubois Natalia Prevarskaya Juan A. Rosado
author_sort	Jose Sanchez-Collado
title	Role of Orai3 in the Pathophysiology of Cancer
title_short	Role of Orai3 in the Pathophysiology of Cancer
title_full	Role of Orai3 in the Pathophysiology of Cancer
title_fullStr	Role of Orai3 in the Pathophysiology of Cancer
title_full_unstemmed	Role of Orai3 in the Pathophysiology of Cancer
title_sort	role of orai3 in the pathophysiology of cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/00de6fa110e14c78983b91618feee454
work_keys_str_mv	AT josesanchezcollado roleoforai3inthepathophysiologyofcancer AT isaacjardin roleoforai3inthepathophysiologyofcancer AT josejlopez roleoforai3inthepathophysiologyofcancer AT victorronco roleoforai3inthepathophysiologyofcancer AT ginesmsalido roleoforai3inthepathophysiologyofcancer AT charlottedubois roleoforai3inthepathophysiologyofcancer AT nataliaprevarskaya roleoforai3inthepathophysiologyofcancer AT juanarosado roleoforai3inthepathophysiologyofcancer
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Role of Orai3 in the Pathophysiology of Cancer

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