Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), intracellular calcium (Ca2+) release channels, fulfill key functions in cell death and survival processes, whose dysregulation contributes to oncogenesis. This is essentially due to the presence of IP3Rs in microdomains of the endoplasmic reticulum (ER) in close proximity to the mitochondria. As such, IP3Rs enable efficient Ca2+ transfers from the ER to the mitochondria, thus regulating metabolism and cell fate. This review focuses on one of the three IP3R isoforms, the type 3 IP3R (IP3R3), which is linked to proapoptotic ER-mitochondrial Ca2+ transfers. Alterations in IP3R3 expression have been highlighted in numerous cancer types, leading to dysregulations of Ca2+ signaling and cellular functions. However, the outcome of IP3R3-mediated Ca2+ transfers for mitochondrial function is complex with opposing effects on oncogenesis. IP3R3 can either suppress cancer by promoting cell death and cellular senescence or support cancer by driving metabolism, anabolic processes, cell cycle progression, proliferation and invasion. The aim of this review is to provide an overview of IP3R3 dysregulations in cancer and describe how such dysregulations alter critical cellular processes such as proliferation or cell death and survival. Here, we pose that the IP3R3 isoform is not only linked to proapoptotic ER-mitochondrial Ca2+ transfers but might also be involved in prosurvival signaling.

中文翻译：

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3型IP3受体：癌症中的变色龙。

肌醇1,4,5-三磷酸（IP3）受体（IP3Rs），细胞内钙（Ca2 +）释放通道在细胞死亡和存活过程中起关键作用，其失调有助于肿瘤发生。这主要归因于IP3Rs在线粒体附近的内质网（ER）的微区中存在。这样，IP3Rs可使Ca2 +从ER高效转移到线粒体，从而调节新陈代谢和细胞命运。这篇综述着眼于三种IP3R同工型之一，即3型IP3R（IP3R3），其与促凋亡的ER-线粒体Ca2 +转移相关。IP3R3表达的改变已在许多癌症类型中得到强调，从而导致Ca2 +信号传导和细胞功能异常。然而，IP3R3介导的Ca2 +转移对线粒体功能的影响是复杂的，并且对肿瘤发生有相反的影响。IP3R3可以通过促进细胞死亡和细胞衰老来抑制癌症，也可以通过驱动新陈代谢，合成代谢过程，细胞周期进程，增殖和侵袭来支持癌症。这篇综述的目的是概述IP3R3在癌症中的失调，并描述这种失调如何改变关键的细胞过程，例如增殖或细胞死亡和存活。在这里，我们提出IP3R3同工型不仅与促凋亡的ER线粒体Ca2 +转移相关，而且可能还参与了生存信号转导。细胞周期进程，增殖和侵袭。这篇综述的目的是概述IP3R3在癌症中的失调，并描述这种失调如何改变关键的细胞过程，例如增殖或细胞死亡和存活。在这里，我们提出IP3R3同工型不仅与促凋亡的ER线粒体Ca2 +转移相关，而且可能还参与了生存信号转导。细胞周期进程，增殖和侵袭。这篇综述的目的是概述IP3R3在癌症中的失调，并描述这种失调如何改变关键的细胞过程，例如增殖或细胞死亡和存活。在这里，我们提出IP3R3同工型不仅与促凋亡的ER线粒体Ca2 +转移相关，而且可能还参与了生存信号转导。