Orai1 plays a critical role in Orai3 synthesis and stability in luminal breast cancer cells
Orai family members are the pore-forming subunits of the Ca2+ release-activated Ca2+ (CRAC) channels that mediate store-operated Ca2+ entry (SOCE), a major mechanism for Ca2+ influx controlled by the filling state of the intracellular Ca2+ stores, that regulates a variety of cellular processes. Whil...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/412208 |
| Acceso en línea: | http://hdl.handle.net/10261/412208 https://api.elsevier.com/content/abstract/scopus_id/105020027111 |
| Access Level: | acceso abierto |
| Palabra clave: | Luminal breast cancer cells Orai1 Orai3 Store-operated Ca(2+) entry |
| Sumario: | Orai family members are the pore-forming subunits of the Ca2+ release-activated Ca2+ (CRAC) channels that mediate store-operated Ca2+ entry (SOCE), a major mechanism for Ca2+ influx controlled by the filling state of the intracellular Ca2+ stores, that regulates a variety of cellular processes. While Orai1 plays a predominant role in SOCE, in luminal breast cancer cells, such as the MCF-7 cell line, SOCE is strongly dependent on Orai3. Using Orai1-knockout (KO) MCF-7 cells or silencing the expression of Orai1 by RNAi in wild-type MCF-7 or T47D cells we show that Orai1 plays a relevant functional role in the regulation of Orai3 expression, thus influencing SOCE. Transfection of Orai1-KO MCF-7 cells with Orai1α expression plasmid induces recovery of Orai1α that initially is not associated to changes in Orai3 protein levels or SOCE but after 7 days results in recovery of Orai3 protein content and SOCE. In Orai1-deficient MCF-7 cells, Orai3 protein synthesis was found to be attenuated, while Orai3 endo-lysosomal degradation was enhanced. Furthermore, Orai1 regulates the expression of estrogen receptor alpha (ERα), which has been associated to Orai3 expression in luminal breast cancer cells. Orai1 induces NFAT2 nuclear translocation in MCF-7 cells and NFAT2 overexpression attenuates ERα and Orai3 protein content in cells expressing Orai1. Our findings show that Orai1 is functionally associated with sustaining Orai3 synthesis and stability and ERα expression in luminal breast cancer cells, consequently modulating the ERα-Orai3 axis, rather than acting as a primary SOCE component. |
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