Fructose metabolism is increasingly recognized as a preferred energy source for cancer cell proliferation. However, it remains unclear why cancer cells favor fructose metabolism and how they acquire a sufficient amount of fructose. Here we report that cancer cells convert glucose into fructose through intra- and extracellular polyol pathways. The fructose metabolism bypasses normal aerobic respiration's self-control to supply excessive metabolites to glycolysis and promotes the Warburg effect. Inhibition of fructose production drastically suppressed glycolysis and ATP production in cancer. Furthermore, we determined that a glucose transporter, SLC2A8/GLUT8, exports intracellular fructose to other cells in the tumor microenvironment. Taken together, our study suggests that the Warburg effect is achieved by means of fructose metabolism, instead of glucose metabolism alone.

中文翻译：

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果糖代谢助长Warburg效应

果糖代谢日益被认为是癌细胞增殖的首选能源。然而，尚不清楚为什么癌细胞促进果糖代谢以及它们如何获得足够量的果糖。在这里，我们报道癌细胞通过细胞内和细胞外多元醇途径将葡萄糖转化为果糖。果糖代谢会绕过正常的有氧呼吸的自我控制，从而为糖酵解提供过多的代谢产物并促进Warburg效应。果糖产生的抑制作用显着抑制了癌症中的糖酵解和ATP产生。此外，我们确定葡萄糖转运蛋白SLC2A8 / GLUT8将细胞内果糖输出到肿瘤微环境中的其他细胞。两者合计，我们的研究表明，通过果糖代谢可以实现Warburg效应，