STIM-IP3R串扰调控乳腺癌细胞的迁移。

IF 6.4 1区生物学 Q1 CELL BIOLOGY

Journal of Cell Biology Pub Date : 2025-07-28 DOI:10.1083/jcb.202411203

Ruslana Militsin,Hadas Achildiev Cohen,Maya Hershfinkel,Ofek Levi,Stavit Drori,Adi Yifat Raz,Yuval Shaked,Raz Palty

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引用次数: 0

摘要

钙离子（Ca2+）是重要的第二信使，参与许多过程，包括肿瘤发生和癌细胞迁移。先前的研究表明，内质网（ER） Ca2+传感器，基质相互作用分子STIM1和STIM2是癌细胞迁移的关键调节因子。在这项研究中，使用缺乏一种或两种STIM亚型的乳腺癌细胞，我们发现尽管STIM蛋白是细胞迁移的关键调节因子，但它们对于这种细胞活动是必不可少的。这种复杂作用的机制涉及STIM蛋白和肌醇1,4,5-三磷酸受体（IP3Rs）之间的功能性串扰。我们的研究结果表明，除了它们在存储操作的Ca2+进入中的经典作用外，STIM蛋白还塑造了ip3r介导的Ca2+释放的空间动力学。我们的研究结果表明，在ER Ca2+耗尽后，活化的STIM蛋白将ip3r介导的Ca2+释放模式从促进细胞迁移的局部信号转变为更扩散的信号，从而减弱细胞迁移。

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STIM-IP3R crosstalk regulates migration of breast cancer cells.

Calcium ions (Ca2+) are crucial second messengers involved in numerous processes including tumorigenesis and cancer cell migration. Previous studies have shown that the endoplasmic reticulum (ER) Ca2+ sensors, stromal interaction molecules STIM1 and STIM2, are key regulators of cancer cell migration. In this study, using breast cancer cells lacking one or both STIM isoforms we show that although STIM proteins are critical regulators of cell migration, they are dispensable for this cellular activity. The mechanism underlying this complex effect involves functional crosstalk between STIM proteins and inositol 1,4,5-trisphosphate receptors (IP3Rs). Our findings indicate that beyond their classical role in store-operated Ca2+ entry, STIM proteins shape the spatial dynamics of IP3R-mediated Ca2+ release. Our results suggest that following ER Ca2+ depletion, the activated STIM proteins shift the pattern of IP3R-mediated Ca2+ release from a localized signal, which promotes cell migration, to a more diffuse signal, which attenuates cell migration.

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来源期刊

Journal of Cell Biology 生物-细胞生物学

CiteScore

12.60

自引率

2.60%

发文量

213

审稿时长

1 months

期刊介绍： The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.