Endoplasmic Reticulum-Mitochondrial Ca(2+) Fluxes Underlying Cancer Cell Survival.
Endoplasmic Reticulum-Mitochondrial Ca(2+) Fluxes Underlying Cancer Cell Survival.
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DOI：
10.3389/fonc.2017.00070
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发表时间：
2017
影响因子：
4.7
通讯作者：
Bultynck G
中科院分区：
文献类型：
--
作者：
Ivanova H;Kerkhofs M;La Rovere RM;Bultynck G
钙离子(Ca~(2+))是癌细胞失控增殖过程中线粒体功能代谢所必需的关键的、普遍存在的细胞内第二信使。线粒体和内质网(ER)通过线粒体相关的ER膜(MAM)连接在一起，ER-线粒体钙离子转移发生在这里，影响与细胞生存、自噬、新陈代谢、细胞死亡敏感性和转移相关的线粒体生物学，这些都是癌症的标志。癌细胞似乎对这些构成ER-线粒体钙离子流动的生存上瘾，因为它们驱动三羧酸循环和产生核苷合成和正常细胞周期进展所需的线粒体底物。此外，线粒体钙单转运体和线粒体钙离子与低氧诱导因子1α信号转导相关联，促进肿瘤的转移和侵袭过程，但它们也可以促进癌基因和复制诱导的细胞衰老。最后，适当的内质网-线粒体钙离子转移似乎是暴露于化疗药物的癌细胞死亡反应中的一个关键事件。在这篇综述中，我们讨论了内质网-线粒体钙离子通量在这些癌症相关特征中的作用。
Calcium ions (Ca2+) are crucial, ubiquitous, intracellular second messengers required for functional mitochondrial metabolism during uncontrolled proliferation of cancer cells. The mitochondria and the endoplasmic reticulum (ER) are connected via “mitochondria-associated ER membranes” (MAMs) where ER–mitochondria Ca2+ transfer occurs, impacting the mitochondrial biology related to several aspects of cellular survival, autophagy, metabolism, cell death sensitivity, and metastasis, all cancer hallmarks. Cancer cells appear addicted to these constitutive ER–mitochondrial Ca2+ fluxes for their survival, since they drive the tricarboxylic acid cycle and the production of mitochondrial substrates needed for nucleoside synthesis and proper cell cycle progression. In addition to this, the mitochondrial Ca2+ uniporter and mitochondrial Ca2+ have been linked to hypoxia-inducible factor 1α signaling, enabling metastasis and invasion processes, but they can also contribute to cellular senescence induced by oncogenes and replication. Finally, proper ER–mitochondrial Ca2+ transfer seems to be a key event in the cell death response of cancer cells exposed to chemotherapeutics. In this review, we discuss the emerging role of ER–mitochondrial Ca2+ fluxes underlying these cancer-related features.