Payen Valéry L, Brisson Lucie, Dewhirst Mark W, Sonveaux Pierre
From the *Pole of Pharmacology & Therapeutics, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL) Medical School, Brussels, Belgium; and †Departments of Radiation Oncology and Pathology, Duke University Medical Center, Durham, NC.
Cancer J. 2015 Mar-Apr;21(2):75-87. doi: 10.1097/PPO.0000000000000098.
Hypoxia is a characteristic of tumors and wounds. Hypoxic cells develop 2 common strategies to face hypoxia: the glycolytic switch and the angiogenic switch. At the onset of hypoxia, alleviation of the Pasteur effect ensures short-term cell survival. Long-term hypoxic cell survival requires a further acceleration of the glycolytic flux under the control of hypoxia-inducible factor 1 that stimulates the expression of most glycolytic transporters and enzymes, uncouples glycolysis from the TCA cycle, and rewires glycolysis to lactic fermentation. Hypoxic cells also trigger angiogenesis, a process that aims to restore normal microenvironmental conditions. Transcription factors (hypoxia-inducible factor 1, nuclear factor κB, activator protein 1) and lactate cooperate to stimulate the expression of proangiogenic agents. Cancer cells differ from normal hypoxic cells by their proliferative agenda and by a high metabolic heterogeneity. These effects in tumor account for further molecular and metabolic changes and for a persistent stimulation of angiogenesis.
缺氧是肿瘤和伤口的一个特征。缺氧细胞会形成两种常见的应对缺氧的策略：糖酵解转换和血管生成转换。在缺氧开始时，巴斯德效应的缓解确保了细胞的短期存活。长期缺氧细胞存活需要在缺氧诱导因子1的控制下进一步加速糖酵解通量，该因子刺激大多数糖酵解转运蛋白和酶的表达，使糖酵解与三羧酸循环解偶联，并将糖酵解重定向为乳酸发酵。缺氧细胞还会触发血管生成，这一过程旨在恢复正常的微环境条件。转录因子（缺氧诱导因子1、核因子κB、激活蛋白1）和乳酸共同作用以刺激促血管生成因子的表达。癌细胞与正常缺氧细胞的不同之处在于它们的增殖议程和高度的代谢异质性。肿瘤中的这些效应导致了进一步的分子和代谢变化以及对血管生成的持续刺激。
