Department of Medical, Surgical, Neurological, Metabolic Sciences, and Aging, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Department of Biology, Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA.
Cell Death Dis. 2018 Feb 14;9(2):228. doi: 10.1038/s41419-018-0313-7.
Metabolic flexibility describes the ability of cells to respond or adapt its metabolism to support and enable rapid proliferation, continuous growth, and survival in hostile conditions. This dynamic character of the cellular metabolic network appears enhanced in cancer cells, in order to increase the adaptive phenotype and to maintain both viability and uncontrolled proliferation. Cancer cells can reprogram their metabolism to satisfy the energy as well as the biosynthetic intermediate request and to preserve their integrity from the harsh and hypoxic environment. Although several studies now recognize these reprogrammed activities as hallmarks of cancer, it remains unclear which are the pathways involved in regulating metabolic plasticity. Recent findings have suggested that carnitine system (CS) could be considered as a gridlock to finely trigger the metabolic flexibility of cancer cells. Indeed, the components of this system are involved in the bi-directional transport of acyl moieties from cytosol to mitochondria and vice versa, thus playing a fundamental role in tuning the switch between the glucose and fatty acid metabolism. Therefore, the CS regulation, at both enzymatic and epigenetic levels, plays a pivotal role in tumors, suggesting new druggable pathways for prevention and treatment of human cancer.
代谢灵活性描述了细胞响应或适应其代谢以支持和实现快速增殖、持续生长和在恶劣条件下生存的能力。细胞代谢网络的这种动态特性似乎在癌细胞中得到了增强，以增加适应性表型并维持活力和不受控制的增殖。癌细胞可以重新编程其代谢以满足能量和生物合成中间产物的需求，并保持其在恶劣和缺氧环境中的完整性。尽管现在有几项研究将这些重编程的活动视为癌症的标志，但尚不清楚哪些途径参与调节代谢可塑性。最近的研究结果表明，肉碱系统（CS）可以被认为是精细触发癌细胞代谢灵活性的瓶颈。事实上，该系统的组成部分参与酰基部分从细胞质到线粒体的双向运输，反之亦然，因此在调节葡萄糖和脂肪酸代谢之间的转换方面发挥着重要作用。因此，CS 的调节（在酶和表观遗传水平上）在肿瘤中起着关键作用，为预防和治疗人类癌症提供了新的可用药途径。
