Calcium signals as regulators of ferroptosis in cancer

IF 4.3 2区 生物学 Q2 CELL BIOLOGY Cell calcium Pub Date : 2024-10-29 DOI:10.1016/j.ceca.2024.102966
Ioana Stejerean-Todoran , Christine S. Gibhardt , Ivan Bogeski
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Abstract

The field of ferroptosis research has grown exponentially since this form of cell death was first identified over a decade ago. Ferroptosis, an iron- and ROS-dependent type of cell death, is controlled by various metabolic pathways, including but not limited to redox and calcium (Ca2+) homeostasis, iron fluxes, mitochondrial function and lipid metabolism. Importantly, therapy-resistant tumors are particularly susceptible to ferroptotic cell death, rendering ferroptosis a promising therapeutic strategy against numerous malignancies. Calcium signals are important regulators of both cancer progression and cell death, with recent studies indicating their involvement in ferroptosis. Cells undergoing ferroptosis are characterized by plasma membrane rupture and the formation of nanopores, which facilitate influx of ions such as Ca2+ into the affected cells. Furthermore, mitochondrial Ca²⁺ levels have been implicated in directly influencing the cellular response to ferroptosis. Despite the remarkable progress made in the field, our understanding of the contribution of Ca2+ signals to ferroptosis remains limited. Here, we summarize key connections between Ca²⁺ signaling and ferroptosis in cancer pathobiology and discuss their potential therapeutic significance.

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钙信号是癌症中铁蛋白沉积的调节因子
自十多年前首次发现这种细胞死亡形式以来,铁凋亡研究领域的发展突飞猛进。铁凋亡是一种依赖于铁和 ROS 的细胞死亡形式,由多种代谢途径控制,包括但不限于氧化还原和钙(Ca2+)平衡、铁通量、线粒体功能和脂质代谢。重要的是,耐药性肿瘤特别容易受到铁氧化细胞死亡的影响,这使得铁氧化成为一种治疗多种恶性肿瘤的有前途的策略。钙信号是癌症进展和细胞死亡的重要调节因子,最近的研究表明钙信号参与了铁凋亡。发生铁突变的细胞的特点是质膜破裂并形成纳米孔,这有利于 Ca2+ 等离子流入受影响的细胞。此外,线粒体 Ca²⁺ 的水平也直接影响着细胞对铁中毒的反应。尽管该领域取得了重大进展,但我们对 Ca2+ 信号对铁变态反应的贡献的了解仍然有限。在此,我们总结了癌症病理生物学中 Ca²⁺ 信号传导与铁凋亡之间的关键联系,并讨论了它们的潜在治疗意义。
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来源期刊
Cell calcium
Cell calcium 生物-细胞生物学
CiteScore
8.70
自引率
5.00%
发文量
115
审稿时长
35 days
期刊介绍: Cell Calcium covers the field of calcium metabolism and signalling in living systems, from aspects including inorganic chemistry, physiology, molecular biology and pathology. Topic themes include: Roles of calcium in regulating cellular events such as apoptosis, necrosis and organelle remodelling Influence of calcium regulation in affecting health and disease outcomes
期刊最新文献
Commentary on: Li et al.; Ca2+ transients on the T cell surface trigger rapid integrin activation in a timescale of seconds. Nature Communications (2024) Distribution and calcium signaling function of somatostatin receptor subtypes in rat pituitary Calcium signals as regulators of ferroptosis in cancer GPCR signalling: Yet another variant route in a highly complex road map Does a transmembrane sodium gradient control membrane potential in mammalian mitochondria?
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