Oncogenic viruses and tumor glucose metabolism: like kids in a candy store.
Oncogenic viruses and tumor glucose metabolism: like kids in a candy store.
复制标题
DOI：
10.1158/1535-7163.mct-11-0517
复制
发表时间：
2012-01
影响因子：
5.7
通讯作者：
Khalili K
中科院分区：
文献类型：
--
作者：
Noch E;Khalili K
鉴于慢性或自发性病毒感染和转化导致的多种恶性肿瘤，致癌病毒代表了显著的公共卫生负担。虽然许多病毒介导的细胞转化的分子信号传导途径是已知的，但这些病毒对增殖肿瘤细胞内的代谢信号传导和表型的影响还不太清楚。无论致癌病毒与代谢信号通路的相互作用涉及增强的葡萄糖摄取和糖酵解（转化细胞的标志性特征），还是调节氧化应激的分子通路的失调，病毒都擅长促进肿瘤扩张。通过它们对细胞增殖途径的影响，如PI 3 K和MAPK途径、细胞周期调节蛋白p53和ATM以及细胞应激反应蛋白HIF-1α和AMPK，病毒对关键的代谢信号级联发挥控制作用。此外，致癌病毒通过与葡萄糖转运蛋白（如GLUT 1）和特异性糖酵解酶（包括丙酮酸激酶、葡萄糖6-磷酸脱氢酶和己糖激酶）的直接和间接相互作用调节肿瘤代谢组学特征。通过这些途径，致癌病毒改变了转化细胞的表型特征及其能量利用方法，并且有可能开发新的抗糖酵解疗法来靶向病毒源性恶性肿瘤中这些失调的途径。
Oncogenic viruses represent a significant public health burden in light of the multitude of malignancies resulting from chronic or spontaneous viral infection and transformation. Though many of the molecular signaling pathways underlying virus-mediated cellular transformation are known, the impact of these viruses on metabolic signaling and phenotype within proliferating tumor cells is less well understood. Whether the interaction of oncogenic viruses with metabolic signaling pathways involves enhanced glucose uptake and glycolysis, both hallmark features of transformed cells, or dysregulation of molecular pathways regulating oxidative stress, viruses are adept at facilitating tumor expansion. Through their effects on cell proliferation pathways, such as the PI3K and MAPK pathways, the cell cycle regulatory proteins, p53 and ATM, and the cell stress response proteins, HIF-1α and AMPK, viruses exert control over critical metabolic signaling cascades. Additionally, oncogenic viruses modulate the tumor metabolomic profile through direct and indirect interaction with glucose transporters, such as GLUT1, and specific glycolytic enzymes, including pyruvate kinase, glucose 6-phosphate dehydrogenase, and hexokinase. Through these pathways, oncogenic viruses alter the phenotypic characteristics of transformed cells and their methods of energy utilization, and it may be possible to develop novel anti-glycolytic therapies to target these dysregulated pathways in virus-derived malignancies.