Cairns Rob A
From the Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Cancer J. 2015 Mar-Apr;21(2):56-61. doi: 10.1097/PPO.0000000000000106.
The Warburg effect was first described by Otto Warburg in the 1920s and describes the preferential conversion of glucose to lactate as opposed to its metabolism through the citric acid cycle to fuel oxidative phosphorylation in the mitochondria, even in the presence of oxygen. This phenotype is a common feature of malignant cells and is also observed in some highly proliferative normal tissues. The selective advantage provided by this phenotype is not entirely clear. Adopting this metabolic state may allow tumor cells to balance their need for ATP, biosynthetic precursor molecules, and reducing power in order to respond to growth and proliferation signals and may provide a selective advantage in the hypoxic and acidic microenvironments that are often a feature of solid tumors. Oncogenic signaling pathways and responses to the local microenvironment combine to produce this metabolic phenotype via a number of molecular mechanisms. A better understanding of these mechanisms in both tumor and normal tissues and a more complete understanding of how the Warburg effect interacts with the rest of the tumor metabolic network should provide opportunities for novel clinical intervention.
瓦伯格效应最早由奥托·瓦伯格在20世纪20年代描述，它描述了即使在有氧的情况下，葡萄糖也优先转化为乳酸，而不是通过柠檬酸循环进行代谢以驱动线粒体中的氧化磷酸化。这种表型是恶性细胞的一个常见特征，在一些高度增殖的正常组织中也有观察到。这种表型所提供的选择性优势尚不完全清楚。采用这种代谢状态可能使肿瘤细胞能够平衡其对ATP、生物合成前体分子和还原力的需求，以便对生长和增殖信号作出反应，并可能在实体瘤常见的缺氧和酸性微环境中提供选择性优势。致癌信号通路和对局部微环境的反应通过多种分子机制共同产生这种代谢表型。更好地理解肿瘤组织和正常组织中的这些机制，以及更全面地了解瓦伯格效应如何与肿瘤代谢网络的其他部分相互作用，应该会为新的临床干预提供机会。
