Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA.
Dev Cell. 2020 Apr 20;53(2):199-211.e6. doi: 10.1016/j.devcel.2020.03.005. Epub 2020 Apr 2.
The Warburg effect is one of the metabolic hallmarks of cancer cells, characterized by enhanced glycolysis even under aerobic conditions. This physiological adaptation is associated with metastasis , but we still have a superficial understanding of how it affects cellular processes during embryonic development. Here we report that the neural crest, a migratory stem cell population in vertebrate embryos, undergoes an extensive metabolic remodeling to engage in aerobic glycolysis prior to delamination. This increase in glycolytic flux promotes Yap/Tead signaling, which activates the expression of a set of transcription factors to drive epithelial-to-mesenchymal transition. Our results demonstrate how shifts in carbon metabolism can trigger the gene regulatory circuits that control complex cell behaviors. These findings support the hypothesis that the Warburg effect is a precisely regulated developmental mechanism that is anomalously reactivated during tumorigenesis and metastasis.
瓦博格效应是癌细胞的代谢特征之一，其特征是即使在有氧条件下，糖酵解也增强了。这种生理适应与转移有关，但我们对它如何影响胚胎发育过程中的细胞过程仍然知之甚少。在这里，我们报告说，神经嵴，脊椎动物胚胎中的一种迁移干细胞群，在脱层之前经历了广泛的代谢重塑，以进行有氧糖酵解。糖酵解通量的增加促进 Yap/Tead 信号，激活一组转录因子的表达，驱动上皮间质转化。我们的结果表明，碳代谢的变化如何引发控制复杂细胞行为的基因调控回路。这些发现支持这样一种假设，即瓦博格效应是一种精确调控的发育机制，在肿瘤发生和转移过程中异常激活。
