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Review

Role of Orai3 in the Pathophysiology of Cancer

by
Jose Sanchez-Collado
1,†,
Isaac Jardin
1,†,
Jose J. López
1,*,
Victor Ronco
1,
Gines M. Salido
1,
Charlotte Dubois
2,
Natalia Prevarskaya
2 and
Juan A. Rosado
1,*
1
Cell Physiology Research Group, Department of Physiology, Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, 10003 Caceres, Spain
2
Laboratory of Cell Physiology, INSERM U1003, Laboratory of Excellence Ion Channels Science and Therapeutics, Department of Biology, Faculty of Science and Technologiesa, University of Lille, 59650 Villeneuve d’Ascq, France
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this manuscript.
Int. J. Mol. Sci. 2021, 22(21), 11426; https://doi.org/10.3390/ijms222111426
Submission received: 10 September 2021 / Revised: 18 October 2021 / Accepted: 21 October 2021 / Published: 22 October 2021
(This article belongs to the Special Issue Calcium Channel Regulation in Cancer: Unravelling the Molecular Mechanisms beneath the Membrane)
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Abstract

The mammalian exclusive Orai3 channel participates in the generation and/or modulation of two independent Ca2+ currents, the store-operated current, Icrac, 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 Iarc, 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 Ca2+ influx. In estrogen receptor-positive breast cancer cells and non-small cell lung cancer (NSCLC) cells store-operated Ca2+ 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.
Keywords: orai3; orai1; calcium entry; cancer orai3; orai1; calcium entry; cancer

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MDPI and ACS Style

Sanchez-Collado, J.; Jardin, I.; López, J.J.; Ronco, V.; Salido, G.M.; Dubois, C.; Prevarskaya, N.; Rosado, J.A. Role of Orai3 in the Pathophysiology of Cancer. Int. J. Mol. Sci. 2021, 22, 11426. https://doi.org/10.3390/ijms222111426

AMA Style

Sanchez-Collado J, Jardin I, López JJ, Ronco V, Salido GM, Dubois C, Prevarskaya N, Rosado JA. Role of Orai3 in the Pathophysiology of Cancer. International Journal of Molecular Sciences. 2021; 22(21):11426. https://doi.org/10.3390/ijms222111426

Chicago/Turabian Style

Sanchez-Collado, Jose, Isaac Jardin, Jose J. López, Victor Ronco, Gines M. Salido, Charlotte Dubois, Natalia Prevarskaya, and Juan A. Rosado. 2021. "Role of Orai3 in the Pathophysiology of Cancer" International Journal of Molecular Sciences 22, no. 21: 11426. https://doi.org/10.3390/ijms222111426

APA Style

Sanchez-Collado, J., Jardin, I., López, J. J., Ronco, V., Salido, G. M., Dubois, C., Prevarskaya, N., & Rosado, J. A. (2021). Role of Orai3 in the Pathophysiology of Cancer. International Journal of Molecular Sciences, 22(21), 11426. https://doi.org/10.3390/ijms222111426

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