Fructose metabolism has emerged as a significant contributor to cancer cell proliferation, yet the underlying mechanisms and sources of fructose for cancer cells remain incompletely understood. In this study, we demonstrate that cancer cells can convert glucose into fructose through a process called the AKR1B1-mediated polyol pathway. Inhibiting the endogenous production of fructose through AKR1B1 deletion dramatically suppressed glycolysis, resulting in reduced cancer cell migration, inhibited growth, and the induction of apoptosis and cell cycle arrest. Conversely, the acceleration of endogenous fructose through AKR1B1 overexpression has been shown to significantly enhance cancer cell proliferation and migration with increased S cell cycle progression. Our findings highlight the crucial role of endogenous fructose in cancer cell malignancy and support the need for further investigation into AKR1B1 as a potential cancer therapeutic target.

果糖代谢已成为癌细胞增殖的重要因素，但果糖对癌细胞的潜在机制和来源仍不完全清楚。在这项研究中，我们证明了癌细胞可以通过称为 AKR1B1 介导的多元醇途径的过程将葡萄糖转化为果糖。通过 AKR1B1 缺失抑制果糖的内源性产生，显著抑制糖酵解，导致癌细胞迁移减少，生长受抑制，并诱导细胞凋亡和细胞周期停滞。相反，通过 AKR1B1 过表达加速内源性果糖已被证明会随着 S 细胞周期进程的增加而显着增强癌细胞增殖和迁移。我们的研究结果强调了内源性果糖在癌细胞恶性肿瘤中的关键作用，并支持进一步研究 AKR1B1 作为潜在癌症治疗靶点的必要性。