Costa A S H, Frezza C
Medical Research Council Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, ENG, United Kingdom.
Medical Research Council Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, ENG, United Kingdom.
Int Rev Cell Mol Biol. 2017;332:213-231. doi: 10.1016/bs.ircmb.2017.01.001. Epub 2017 Mar 15.
The process of tumorigenesis can be described by a series of molecular features, among which alteration of cellular metabolism has recently emerged. This metabolic rewiring fulfills the energy and biosynthetic demands of fast proliferating cancer cells and amplifies their metabolic repertoire to survive and proliferate in the poorly oxygenated and nutrient-deprived tumor microenvironment. During the last decade, the complex reprogramming of cancer cell metabolism has been widely investigated, revealing cancer-specific metabolic alterations. These include dysregulation of glucose and glutamine metabolism, alterations of lipid synthesis and oxidation, and a complex rewiring of mitochondrial function. However, mitochondria are not the only metabolically active organelles within the cell, and other organelles, including lysosomes, peroxisomes, and endoplasmic reticulum, harbor components of the metabolic network. Of note, dysregulation of the function of these organelles is increasingly recognized in cancer cells. However, to what extent these organelles contribute to the metabolic reprogramming of cancer is not fully understood. In this review, we describe the main metabolic functions of these organelles and provide insights into how they communicate to orchestrate a coordinated metabolic reprogramming during transformation.
肿瘤发生过程可以通过一系列分子特征来描述，其中细胞代谢的改变最近已显现出来。这种代谢重编程满足了快速增殖的癌细胞的能量和生物合成需求，并扩大了它们的代谢能力，使其能够在缺氧和营养匮乏的肿瘤微环境中存活和增殖。在过去十年中，癌细胞代谢的复杂重编程得到了广泛研究，揭示了癌症特异性的代谢改变。这些改变包括葡萄糖和谷氨酰胺代谢失调、脂质合成和氧化的改变以及线粒体功能的复杂重编程。然而，线粒体并不是细胞内唯一具有代谢活性的细胞器，其他细胞器，包括溶酶体、过氧化物酶体和内质网，也包含代谢网络的组成部分。值得注意的是，这些细胞器功能的失调在癌细胞中越来越受到认可。然而，这些细胞器在多大程度上促成了癌症的代谢重编程尚未完全了解。在这篇综述中，我们描述了这些细胞器的主要代谢功能，并深入探讨了它们如何相互沟通以在细胞转化过程中协调代谢重编程。
