SARAF and EFHB Modulate Store-Operated Ca2+ Entry and Are Required for Cell Proliferation, Migration and Viability in Breast Cancer Cells
| Autor: | Jardin, Isaac, Nieto Felipe, Enrique, Alvarado, Sandra, Diez Bello, Raquel, López, Jose J., Smani Hajami, Tarik, Rosado, Juan Antonio |
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| Přispěvatelé: | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | idUS. Depósito de Investigación de la Universidad de Sevilla instname |
| Popis: | Breast cancer is among the most common malignancies in women. From the molecular point of view, breast cancer can be grouped into different categories, including the luminal (estrogen receptor positive (ER+)) and triple negative subtypes, which show distinctive features and, thus, are sensitive to different therapies. Breast cancer cells are strongly dependent on Ca2+ influx. Storeoperated Ca2+ entry (SOCE) has been found to support a variety of cancer hallmarks including cell viability, proliferation, migration, and metastasis. The Ca2+ channels of the Orai family and the endoplasmic reticulum Ca2+ sensor STIM1 are the essential components of SOCE, but the extent of Ca2+ influx is fine-tuned by several regulatory proteins, such as the STIM1 modulators SARAF and EFHB. Here, we show that the expression and/or function of SARAF and EFHB is altered in breast cancer cells and both proteins are required for cell proliferation, migration, and viability. EFHB expression is upregulated in luminal and triple negative breast cancer (TNBC) cells and is essential for full SOCE in these cells. SARAF expression was found to be similar in breast cancer and pre-neoplastic breast epithelial cells, and SARAF knockdown was found to result in enhanced SOCE in pre-neoplastic and TNBC cells. Interestingly, silencing SARAF expression in ER+ MCF7 cells led to attenuation of SOCE, thus suggesting a distinctive role for SARAF in this cell type. Finally, we used a combination of approaches to show that molecular knockdown of SARAF and EFHB significantly attenuates the ability of breast cancer cells to proliferate and migrate, as well as cell viability. In aggregate, SARAF and EFHB are required for the fine modulation of SOCE in breast cancer cells and play an important role in the maintenance of proliferation, migration, and viability in these cells Agencia Estatal de Investigación PID2019-104084GB-C21/AEI/ 10.13039/501100011033 and PID2019-104084GB-C22/AEI/10.13039/501100011033, MICINN (Grants BFU2016-74932-C2) Junta de Extremadura-Fondo Europeo de Desarrollo Regional (FEDER; Grants IB20007 and GR18061) Junta de Extremadura (TA18054 and TA18011) |
| Databáze: | OpenAIRE |
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