Cancer is a leading cause of death worldwide. All major tumor suppressors and oncogenes are now recognized to have fundamental connections with metabolic pathways. A hallmark feature of cancer cells is a reprogramming of their metabolism even when nutrients are available. Increasing evidence indicates that most cancer cells rely on mitochondrial metabolism to sustain their energetic and biosynthetic demands. Mitochondria are functionally and physically coupled to the endoplasmic reticulum (ER), the major calcium (Ca^2 +) storage organelle in mammalian cells, through special domains known as mitochondria-ER contact sites (MERCS). In this domain, the release of Ca^2 + from the ER is mainly regulated by inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), a family of Ca^2 + release channels activated by the ligand IP3. IP3R mediated Ca^2 + release is transferred to mitochondria through the mitochondrial Ca^2 + uniporter (MCU). Once in the mitochondrial matrix, Ca^2 + activates several proteins that stimulate mitochondrial performance. The role of IP3R and MCU in cancer, as well as the other proteins that enable the Ca^2 + communication between these two organelles is just beginning to be understood. Here, we describe the function of the main players of the ER mitochondrial Ca^2 + communication and discuss how this particular signal may contribute to the rise and development of cancer traits.

癌症是世界范围内的主要死亡原因。所有主要的肿瘤抑制基因和癌基因现在都被认为与代谢途径有基本的联系。癌细胞的一个标志性特征是即使在有营养物质的情况下也会对它们的新陈代谢进行重新编程。越来越多的证据表明，大多数癌细胞依靠线粒体代谢来维持其能量和生物合成需求。线粒体通过称为线粒体-ER 接触位点 (MERCS) 的特殊结构域在功能上和物理上与哺乳​​动物细胞中主要的钙 (Ca ^{2  + ) 储存细胞器内质网 (ER) 耦合。}在该域中，Ca ^{2  +}来自 ER 的主要受肌醇 1,4,5-三磷酸 (IP3) 受体 (IP3Rs) 调节，这是一个由配体 IP3 激活的 Ca ^{2  +}释放通道家族。IP3R 介导的 Ca ^{2  +}释放通过线粒体 Ca ^{2  +}单向转运体 (MCU) 转移到线粒体。一旦进入线粒体基质，Ca ^{2  +}就会激活几种刺激线粒体性能的蛋白质。IP3R 和 MCU 在癌症中的作用，以及使这两个细胞器之间的 Ca ^{2  +}通信成为可能的其他蛋白质才刚刚开始被理解。在这里，我们描述了 ER 线粒体 Ca ^{2  +主要参与者的功能}交流并讨论这种特殊信号如何促进癌症特征的产生和发展。