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糖氨基甘氨酸驱动的脂蛋白吸收保护瘤免受铁

Dylan Calhoon ¹, Lingjie Sang ¹, Fubo Ji ¹

¹Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
²Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
³Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA.
⁴Quantitative Biomedical Research Center, Peter O'Donnell School of Public Health, University of Texas Southwestern, Dallas, TX, USA.
⁵Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁶Kidney Cancer Program, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁷Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
⁸Scripps Center for Metabolomics, The Scripps Research Institute, La Jolla, CA, USA.
⁹Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁰Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹¹Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.
¹²Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹³Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. Javier.GarciaBermudez@UTSouthwestern.edu.

⁰Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Nature +

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2025年六月11日

在PubMed上查看摘要

概括

癌细胞使用脂蛋白来阻断细胞死亡的途径. 这一过程依赖于硫酸糖氨基酸 (GAG),并提供维生素E,为癌症治疗提供了潜在的治疗点.

科学领域

癌症生物学
细胞代谢
脂质生物化学

背景情况

脂质对癌细胞结构和信号传递至关重要.
癌细胞经常进口细胞外脂质以满足代谢需求.
进口脂质在癌症进展中的作用尚未完全理解.

研究的目的

研究细胞外脂质吸收在癌症中的作用.
在癌症中确定调节铁死敏感性的机制.
探索脂蛋白吸收作为癌细胞命运的决定因素.

主要方法

功能性遗传查以确定铁症敏感性的关键决定因素.
对各种癌症类型的脂蛋白补充测定.
在脂蛋白摄取中分析硫酸氨基甘油 (GAG) 和蛋白甘油.
在小鼠体内瘤生长研究.
对人类清细胞细胞癌和正常脏组织进行比较分析.

主要成果

脂蛋白吸收是决定癌症中铁变敏感性的关键因素.
用脂蛋白补充剂可以抑制各种癌症类型的铁.
脂蛋白提供α-托科菲罗尔 (维生素E),它调解了抗ferroptotic作用.
癌细胞利用GAG依赖的途径,涉及细胞表面蛋白质,以吸收脂蛋白.
干扰GAG生物合成或表面GAG使癌细胞对铁亡敏感,并阻碍瘤生长.
人类清晰细胞细胞癌显示GAG和脂蛋白衍生α-托科菲醇的增加.

结论

在癌症中,脂蛋白吸收起着显著的抗ferroptotic机制作用.
脂肪蛋白吸收的GAG依赖途径对于癌细胞的存活至关重要.
向GAG生物合成是一个潜在的治疗策略,用于增强癌症中的铁.

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