Physiological functions of calcium signaling via Orai1 in cancer
Abstract Intracellular calcium (Ca2+) signaling regulates many cellular functions, including cell proliferation and migration, in both normal cells and cancer cells. Store-operated Ca2+ entry (SOCE) is a major mechanism by which Ca2+ is imported from the extracellular space to the intracellular spac...
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Elsevier
2023-09-01
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| Series: | Journal of Physiological Sciences |
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| Online Access: | https://doi.org/10.1186/s12576-023-00878-0 |
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| author | Masanari Umemura Rina Nakakaji Yoshihiro Ishikawa |
| author_facet | Masanari Umemura Rina Nakakaji Yoshihiro Ishikawa |
| author_sort | Masanari Umemura |
| collection | DOAJ |
| description | Abstract Intracellular calcium (Ca2+) signaling regulates many cellular functions, including cell proliferation and migration, in both normal cells and cancer cells. Store-operated Ca2+ entry (SOCE) is a major mechanism by which Ca2+ is imported from the extracellular space to the intracellular space, especially in nonexcitable cells. Store-operated Ca2+ entry (SOCE) is also a receptor-regulated Ca2+ entry pathway that maintains Ca2+ homeostasis by sensing reduced Ca2+ levels in the endoplasmic reticulum (ER). In general, the activation of G protein-coupled receptors (GPCRs) or immunoreceptors, such as T-cell, B-cell and Fc receptors, results in the production of inositol 1,4,5-trisphosphate (IP3). IP3 binds to IP3 receptors located in the ER membrane. The, IP3 receptors in the ER membrane trigger a rapid and transient release of Ca2+ from the ER store. The resulting depletion of ER Ca2+ concentrations is sensed by the EF-hand motif of stromal interaction molecule (STIM), i.e., calcium sensor, which then translocates to the plasma membrane (PM). STIM interacts with Orai Ca2+ channel subunits (also known as CRACM1) on the PM, leading to Ca2+ influx from the extracellular space to increase intracellular Ca2+ concentrations. The physiological functions of Orai and STIM have been studied mainly with respect to their roles in the immune system. Based on numerous previous studies, Orai channels (Orai1, Orai2 and Orai3 channels) control Ca2+ release-activated Ca2+ (CRAC) currents and contribute to SOCE currents in other types of cells, including various cancer cells. There are many reports that Orai1 is involved in cell proliferation, migration, metastasis, apoptosis and epithelial–mesenchymal transition (EMT) in various cancers. We previously found that Orai1 plays important roles in cell apoptosis and migration in melanoma. Recently, we reported novel evidence of Orai1 in human oral squamous cell carcinoma (OSCC) cells and human cardiac fibroblasts (HCFs). In this review, we present multiple physiological functions of Orai1 in various cancer cells and cardiac fibroblasts, including our findings. |
| format | Article |
| id | doaj-art-64fcde40fd514906bf2df1e75e30a656 |
| institution | OA Journals |
| issn | 1880-6562 |
| language | English |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Physiological Sciences |
| spelling | doaj-art-64fcde40fd514906bf2df1e75e30a6562025-08-20T02:06:39ZengElsevierJournal of Physiological Sciences1880-65622023-09-0173111110.1186/s12576-023-00878-0Physiological functions of calcium signaling via Orai1 in cancerMasanari Umemura0Rina Nakakaji1Yoshihiro Ishikawa2Cardiovascular Research Institute, Yokohama City University Graduate School of MedicineCardiovascular Research Institute, Yokohama City University Graduate School of MedicineCardiovascular Research Institute, Yokohama City University Graduate School of MedicineAbstract Intracellular calcium (Ca2+) signaling regulates many cellular functions, including cell proliferation and migration, in both normal cells and cancer cells. Store-operated Ca2+ entry (SOCE) is a major mechanism by which Ca2+ is imported from the extracellular space to the intracellular space, especially in nonexcitable cells. Store-operated Ca2+ entry (SOCE) is also a receptor-regulated Ca2+ entry pathway that maintains Ca2+ homeostasis by sensing reduced Ca2+ levels in the endoplasmic reticulum (ER). In general, the activation of G protein-coupled receptors (GPCRs) or immunoreceptors, such as T-cell, B-cell and Fc receptors, results in the production of inositol 1,4,5-trisphosphate (IP3). IP3 binds to IP3 receptors located in the ER membrane. The, IP3 receptors in the ER membrane trigger a rapid and transient release of Ca2+ from the ER store. The resulting depletion of ER Ca2+ concentrations is sensed by the EF-hand motif of stromal interaction molecule (STIM), i.e., calcium sensor, which then translocates to the plasma membrane (PM). STIM interacts with Orai Ca2+ channel subunits (also known as CRACM1) on the PM, leading to Ca2+ influx from the extracellular space to increase intracellular Ca2+ concentrations. The physiological functions of Orai and STIM have been studied mainly with respect to their roles in the immune system. Based on numerous previous studies, Orai channels (Orai1, Orai2 and Orai3 channels) control Ca2+ release-activated Ca2+ (CRAC) currents and contribute to SOCE currents in other types of cells, including various cancer cells. There are many reports that Orai1 is involved in cell proliferation, migration, metastasis, apoptosis and epithelial–mesenchymal transition (EMT) in various cancers. We previously found that Orai1 plays important roles in cell apoptosis and migration in melanoma. Recently, we reported novel evidence of Orai1 in human oral squamous cell carcinoma (OSCC) cells and human cardiac fibroblasts (HCFs). In this review, we present multiple physiological functions of Orai1 in various cancer cells and cardiac fibroblasts, including our findings.https://doi.org/10.1186/s12576-023-00878-0CalciumOrai1EP4Store-operated-calcium entry (SOCE)CancerCardiac fibroblast |
| spellingShingle | Masanari Umemura Rina Nakakaji Yoshihiro Ishikawa Physiological functions of calcium signaling via Orai1 in cancer Journal of Physiological Sciences Calcium Orai1 EP4 Store-operated-calcium entry (SOCE) Cancer Cardiac fibroblast |
| title | Physiological functions of calcium signaling via Orai1 in cancer |
| title_full | Physiological functions of calcium signaling via Orai1 in cancer |
| title_fullStr | Physiological functions of calcium signaling via Orai1 in cancer |
| title_full_unstemmed | Physiological functions of calcium signaling via Orai1 in cancer |
| title_short | Physiological functions of calcium signaling via Orai1 in cancer |
| title_sort | physiological functions of calcium signaling via orai1 in cancer |
| topic | Calcium Orai1 EP4 Store-operated-calcium entry (SOCE) Cancer Cardiac fibroblast |
| url | https://doi.org/10.1186/s12576-023-00878-0 |
| work_keys_str_mv | AT masanariumemura physiologicalfunctionsofcalciumsignalingviaorai1incancer AT rinanakakaji physiologicalfunctionsofcalciumsignalingviaorai1incancer AT yoshihiroishikawa physiologicalfunctionsofcalciumsignalingviaorai1incancer |