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.
癌细胞的有氧糖酵解现象，最初由Warburg于一百年前发现，即使在氧气充足条件下仍以乳酸作为葡萄糖分解的最终产物，这一发现构成了当前对癌细胞特异性代谢途径重编程研究热潮的基石。如今学界对癌细胞代谢的关注已远超糖酵解相关的原始Warburg效应，延伸至包括氨基酸代谢、一碳代谢、磷酸戊糖途径、核苷酸合成及抗氧化机制等多元代谢通路。鉴于葡萄糖和氨基酸是驱动癌细胞代谢途径改变的核心营养物质，介导这些营养物质及其代谢产物跨膜转运的载体蛋白——不仅跨越质膜，还涉及线粒体膜和溶酶体膜——已成为Warburg效应扩展体系的重要组成部分。本综述聚焦于这些转运蛋白与代谢通路间的相互作用如何促进代谢重编程这一癌细胞标志性特征的形成。近期对Warburg效应独特代谢特征的新认知，其重要价值在于为开发新一代抗癌疗法识别出创新药物靶点。
肿瘤(癌症)患者之家