ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Orai3 is an estrogen receptor α-regulated Ca²⁺ channel that promotes tumorigenesis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 186 citations in OpenAlex.
- TRP Channels Interactome as a Novel Therapeutic Target in Breast Cancer.Frontiers in oncology · 2021Pooled it
- The CaThe Journal of biological chemistry · 2026Article
- Platelet-derived mitochondrial transfer in cancer metastasis: mechanisms, functional consequences, and translational opportunities.Clinical & experimental metastasis · 2026Review
- A Quartet of Native Orai Channel Isoforms Orchestrates Graded NFAT Activation and Transcription.bioRxiv : the preprint server for biology · 2026Article
- NFATc1 drives Orai3 transcription and proteolysis by harnessing epigenome differences in the MARCH8 promoter.The EMBO journal · 2025Article
- Targeting Ion Channels for Cancer Therapy: From Pathophysiological Mechanisms to Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Store-operated calcium entry-based targets for novel cancer therapeutic development.The Journal of pharmacology and experimental therapeutics · 2025Review
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Review of electrophysiological models to study membrane potential changes in breast cancer cell transformation and tumor progression.Frontiers in physiology · 2025Review
- Orai1 and Orai3 act through distinct signalling axes to promote stemness and tumorigenicity of breast cancer stem cells.Stem cell research & therapy · 2024Article
- Vulnerability of Store-Operated Calcium Entry to Inhibitors and Microenvironment in Cells of Different Breast Cancer Subtypes.Life (Basel, Switzerland) · 2024Article
- Article
- NNAT is a novel mediator of oxidative stress that suppresses ER + breast cancer.Molecular medicine (Cambridge, Mass.) · 2023Article
- Review
- Too much of a good thing: The case of SOCE in cellular apoptosis.Cell calcium · 2023Review
- CRAC and SK Channels: Their Molecular Mechanisms Associated with Cancer Cell Development.Cancers · 2022Review
- Orai3 mediates Orai channel remodelling to activate fibroblast in pulmonary fibrosis.Journal of cellular and molecular medicine · 2022Article
- Science CommuniCaCells · 2022Review
- Photopharmacological modulation of native CRAC channels using azoboronate photoswitches.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mitofusin-2 Negatively Regulates Melanogenesis by Modulating Mitochondrial ROS Generation.Cells · 2022Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Store-operated Ca(2+) entry (SOCE) encoded by Orai1 proteins is a ubiquitous Ca(2+)-selective conductance involved in cellular proliferation and migration. We recently described up-regulation of Orai3 channels that selectively mediate SOCE in estrogen receptor α-expressing (ERα(+)) breast cancer cells. However, the connection between ERα and Orai3 and the role of Orai3 in tumorigenesis remain unknown. Here, we show that ERα knockdown decreases Orai3 mRNA (by ∼63%) and protein (by ∼44%) with no effect on Orai1. ERα knockdown decreases Orai3-mediated SOCE (by ∼43%) and the corresponding Ca(2+) release-activated Ca(2+) (CRAC) current (by ∼42%) in ERα(+) MCF7 cells. The abrogation of SOCE in MCF7 cells on ERα knockdown can be rescued by ectopic expression of Orai3. ERα activation increased Orai3 expression and SOCE in MCF7 cells. Epidermal growth factor (EGF) and thrombin stimulate Ca(2+) influx into MCF7 cells through Orai3. Orai3 knockdown inhibited SOCE-dependent phosphorylation of extracellular signal-regulated kinase (ERK1/2; by ∼44%) and focal adhesion kinase (FAK; by ∼46%) as well as transcriptional activity of nuclear factor for activated T cells (NFAT; by ∼49%). Significantly, Orai3 knockdown selectively decreased anchorage-independent growth (by ∼58%) and Matrigel invasion (by ∼44%) of ERα(+) MCF7 cells with no effect on ERα(-) MDA-MB231 cells. Moreover, Orai3 knockdown inhibited ERα(+) cell tumorigenesis in immunodeficient mice (∼66% reduction in tumor volume). These data establish Orai3 as an ERα-regulated channel and a potential selective therapeutic target for ERα(+) breast cancers.
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