Mathew Marilyn, Nguyen Nhi T, Bhutia Yangzom D, Sivaprakasam Sathish, Ganapathy Vadivel
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Cancers (Basel). 2024 Jan 24;16(3):504. doi: 10.3390/cancers16030504.
Aerobic glycolysis in cancer cells, originally observed by Warburg 100 years ago, which involves the production of lactate as the end product of glucose breakdown even in the presence of adequate oxygen, is the foundation for the current interest in the cancer-cell-specific reprograming of metabolic pathways. The renewed interest in cancer cell metabolism has now gone well beyond the original Warburg effect related to glycolysis to other metabolic pathways that include amino acid metabolism, one-carbon metabolism, the pentose phosphate pathway, nucleotide synthesis, antioxidant machinery, etc. Since glucose and amino acids constitute the primary nutrients that fuel the altered metabolic pathways in cancer cells, the transporters that mediate the transfer of these nutrients and their metabolites not only across the plasma membrane but also across the mitochondrial and lysosomal membranes have become an integral component of the expansion of the Warburg effect. In this review, we focus on the interplay between these transporters and metabolic pathways that facilitates metabolic reprogramming, which has become a hallmark of cancer cells. The beneficial outcome of this recent understanding of the unique metabolic signature surrounding the Warburg effect is the identification of novel drug targets for the development of a new generation of therapeutics to treat cancer.
癌细胞中的有氧糖酵解，最初是由瓦尔堡在100年前观察到的，即使在有充足氧气的情况下，它也会将乳酸作为葡萄糖分解的最终产物产生，这是当前对癌细胞特异性代谢途径重编程产生兴趣的基础。目前对癌细胞代谢的重新关注已经远远超出了最初与糖酵解相关的瓦尔堡效应，扩展到了其他代谢途径，包括氨基酸代谢、一碳代谢、磷酸戊糖途径、核苷酸合成、抗氧化机制等。由于葡萄糖和氨基酸是为癌细胞中改变的代谢途径提供燃料的主要营养物质，介导这些营养物质及其代谢产物不仅跨质膜，而且跨线粒体膜和溶酶体膜转运的转运蛋白，已成为瓦尔堡效应扩展的一个不可或缺的组成部分。在这篇综述中，我们重点关注这些转运蛋白与促进代谢重编程的代谢途径之间的相互作用，而代谢重编程已成为癌细胞的一个标志。最近对围绕瓦尔堡效应的独特代谢特征的理解所带来的有益成果，是确定了用于开发新一代癌症治疗药物的新靶点。
