Ion channels in particular Calcium (Ca²⁺) channels play a critical role in physiology by regulating plethora of cellular processes ranging from cell proliferation, differentiation, transcriptional regulation and programmed cell death. One such physiologically important and highly Ca²⁺ selective channel family is Orai channels consisting of three homologs Orai1, Orai2 and Orai3. Orai channels are responsible for Ca²⁺ influx across the plasma membrane in response to decrease in Endoplasmic Reticulum (ER) Ca²⁺ stores. STIM1/STIM2 proteins sense the reduction in ER Ca²⁺ levels and activate Orai channels for restoring ER Ca²⁺ as well as for driving cellular functions. This signaling cascade is known as Store Operated Ca²⁺ Entry (SOCE). Although Orai1 is the ubiquitous SOCE channel protein, Orai2 and Orai3 mediate SOCE in certain specific tissues. Further, mammalian specific homolog Orai3 forms heteromultimeric channel with Orai1 for constituting Arachidonic acid regulated Ca²⁺ (ARC) channels or arachidonic acid metabolite Leukotriene C₄ (LTC₄) regulated Ca²⁺ (LRC) channels. Literature suggests that Orai3 regulates Breast, Prostate, Lung and Gastrointestinal cancers by either forming Store Operated Ca²⁺ (SOC) or ARC/LRC channels in the cancerous cells but not in healthy tissue. In this review, we would discuss the role of Orai3 in these cancers and would highlight the potential of therapeutic targeting of Orai3 for better management and treatment of cancer. Finally, we will deliberate on key outstanding questions in the field that demand critical attention and further studies.

离子通道，尤其是钙 (Ca ²⁺ ) 通道，通过调节细胞增殖、分化、转录调节和程序性细胞死亡等多种细胞过程，在生理学中发挥关键作用。一个这样的生理上重要且高度 Ca ²⁺选择性通道家族是由三个同源物 Orai1、Orai2 和 Orai3 组成的 Orai 通道。Orai 通道负责响应内质网 (ER) Ca ²⁺储存的减少而导致Ca ²⁺跨质膜流入。STIM1/STIM2 蛋白感知 ER Ca ²⁺水平的降低并激活 Orai 通道以恢复 ER Ca ²⁺以及驱动细胞功能。这种信号级联称为存储操作的 Ca ²⁺条目 (SOCE)。尽管 Orai1 是无处不在的 SOCE 通道蛋白，但 Orai2 和 Orai3 在某些特定组织中介导 SOCE。此外，哺乳动物特异性同源物Orai3与Orai1形成异源多聚体通道，用于构成花生四烯酸调节的Ca ²⁺ (ARC)通道或花生四烯酸代谢物白三烯C ₄ (LTC ₄ )调节的Ca ²⁺ (LRC)通道。文献表明，Orai3 通过形成 Store Operated Ca ²⁺来调节乳腺癌、前列腺癌、肺癌和胃肠道癌(SOC) 或 ARC/LRC 通道在癌细胞中但不在健康组织中。在这篇综述中，我们将讨论 Orai3 在这些癌症中的作用，并强调 Orai3 的治疗靶向在更好地管理和治疗癌症方面的潜力。最后，我们将讨论该领域需要引起高度重视和进一步研究的关键突出问题。