Institute of Developmental Biology and Cancer Research, University of Nice, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue Valombrose, 06189 Nice, France.
Curr Opin Genet Dev. 2011 Feb;21(1):67-72. doi: 10.1016/j.gde.2010.10.006. Epub 2010 Nov 11.
The hypoxia-inducible factor (HIF-1), in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumour cells. This transcription factor not only favours cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. These include epithelial-mesenchymal transition, angiogenesis, autophagy, and synthesis and storage of lipid and glycogen. HIF-1 also ensures survival by correcting tumour acidosis via increased expression of the carbonic anhydrase CA IX and the lactate/H+ symporter MCT4. The targeting of key HIF-1-mediated steps, responsible for exacerbated glycolysis and pHi-control, and of the 'guardian of cellular energy' AMP-kinase should offer novel therapeutic opportunities to fight cancer.
缺氧诱导因子（HIF-1）除了遗传和表观遗传改变外，主要负责缺氧肿瘤细胞中细胞代谢的改变。这种转录因子不仅通过从氧化磷酸化到糖酵解和乳酸生成的代谢转变促进细胞增殖，还通过调节适应性生存机制来刺激营养供应。这些机制包括上皮-间充质转化、血管生成、自噬以及脂质和糖原的合成和储存。HIF-1 还通过增加碳酸酐酶 CAIX 和乳酸/H+转运蛋白 MCT4 的表达来纠正肿瘤酸中毒，从而确保生存。针对关键的 HIF-1 介导的步骤，负责加剧的糖酵解和 pH 值控制，以及“细胞能量守护者”AMP 激酶，应该为对抗癌症提供新的治疗机会。
