Shakya Arvind, Cooksey Robert, Cox James E, Wang Victoria, McClain Donald A, Tantin Dean
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Nat Cell Biol. 2009 Mar;11(3):320-7. doi: 10.1038/ncb1840. Epub 2009 Feb 15.
Cancer cells frequently undergo a shift from oxidative to glycolytic metabolism. Although there is interest in targeting metabolism as a form of cancer therapy, this area still remains in its infancy. Using cells, embryos and adult animals, we show here that loss of the widely expressed transcription factor Oct1 induces a coordinated metabolic shift: mitochondrial activity and amino acid oxidation are increased, while glucose metabolism is reduced. Altered expression of direct Oct1 targets encoding metabolic regulators provides a mechanistic underpinning to these results. We show that these metabolic changes directly oppose tumorigenicity. Collectively, our findings show that Oct1, the genes it regulates and the pathways these genes affect could be used as targets for new modes of cancer therapy.
癌细胞经常经历从氧化代谢到糖酵解代谢的转变。尽管将代谢作为一种癌症治疗形式备受关注，但该领域仍处于起步阶段。我们在此利用细胞、胚胎和成年动物表明，广泛表达的转录因子Oct1的缺失会引发协调的代谢转变：线粒体活性和氨基酸氧化增加，而葡萄糖代谢减少。编码代谢调节因子的Oct1直接靶点的表达改变为这些结果提供了机制基础。我们表明，这些代谢变化直接对抗肿瘤发生。总体而言，我们的研究结果表明，Oct1、它所调控的基因以及这些基因影响的通路可作为新型癌症治疗模式的靶点。
