Mitochondria in cancer: at the crossroads of life and death.
Mitochondria in cancer: at the crossroads of life and death.
复制标题
癌症中的线粒体：在生与死的十字路口。
DOI：
10.5732/cjc.011.10018
复制
发表时间：
2011-08
影响因子：
--
通讯作者：
Mackeigan JP
中科院分区：
文献类型：
--
作者：
Fogg VC;Lanning NJ;Mackeigan JP
线粒体过程在肿瘤的发生和发展中起重要作用。在这篇综述中，我们专注于线粒体功能可能有助于癌症的三个关键过程：通过改变葡萄糖代谢，活性氧（ROS）的产生和内在凋亡功能的妥协。癌症葡萄糖代谢的改变包括瓦尔堡效应，导致代谢从有氧呼吸转向糖酵解，即使存在足够的氧气来支持呼吸。细胞代谢的这种改变可能通过增加细胞生长和增殖所需的生物合成中间体的可用性而有利于肿瘤细胞生长。特定代谢酶，即琥珀酸脱氢酶、富马酸水合酶和异柠檬酸脱氢酶的突变与人类癌症有关。线粒体ROS可能通过DNA损伤和异常信号通路的激活而导致癌症。ROS依赖的转录因子缺氧诱导因子（HIF）的稳定化可能是肿瘤发生的一个特别重要的事件。内源性细胞凋亡功能的受损消除了对抗癌症的重要细胞保护措施，并与肿瘤发生、肿瘤转移和化疗耐药性有关。每一个主要的线粒体过程都是相互联系的。在这篇综述中，我们概述了它们之间的联系，并讨论了这些线粒体途径可能成为癌症治疗的靶点的方法。
Mitochondrial processes play an important role in tumor initiation and progression. In this review, we focus on three critical processes by which mitochondrial function may contribute to cancer: through alterations in glucose metabolism, the production of reactive oxygen species (ROS) and compromise of intrinsic apoptotic function. Alterations in cancer glucose metabolism include the Warburg effect, leading to a shift in metabolism away from aerobic respiration toward glycolysis, even when sufficient oxygen is present to support respiration. Such alterations in cellular metabolism may favor tumor cell growth by increasing the availability of biosynthetic intermediates needed for cellular growth and proliferation. Mutations in specific metabolic enzymes, namely succinate dehydrogenase, fumarate hydratase and the isocitrate dehydrogenases, have been linked to human cancer. Mitochondrial ROS may contribute to cancer via DNA damage and the activation of aberrant signaling pathways. ROS-dependent stabilization of the transcription factor hypoxia-inducible factor (HIF) may be a particularly important event for tumorigenesis. Compromised function of intrinsic apoptosis removes an important cellular safeguard against cancer and has been implicated in tumorigenesis, tumor metastasis, and chemoresistance. Each of the major mitochondrial processes is linked. In this review, we outline the connections between them and address ways these mitochondrial pathways may be targeted for cancer therapy.