Zhao Qing, Han Bing, Wang Lu, Wu Jia, Wang Siliang, Ren Zhenxing, Wang Shouli, Yang Haining, Carbone Michele, Dong Changsheng, Melino Gerry, Chen Wen-Lian, Jia Wei
Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA.
Cell Death Differ. 2024 Dec;31(12):1611-1624. doi: 10.1038/s41418-024-01393-4. Epub 2024 Oct 15.
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一个重要因素，然而癌细胞中果糖的潜在机制和来源仍未完全明确。在本研究中，我们证明癌细胞可通过一种名为AKR1B1介导的多元醇途径将葡萄糖转化为果糖。通过缺失AKR1B1抑制果糖的内源性产生，可显著抑制糖酵解，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，通过过表达AKR1B1加速内源性果糖的产生，已被证明可显著增强癌细胞的增殖和迁移，并增加S期细胞周期进程。我们的研究结果突出了内源性果糖在癌细胞恶性肿瘤中的关键作用，并支持进一步研究将AKR1B1作为潜在癌症治疗靶点的必要性。
