Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Cell Death Dis. 2021 Dec 2;12(12):1124. doi: 10.1038/s41419-021-04416-x.
Glycosylation is an important modification of membrane proteins that results in functional changes in many cellular activities, from cell-cell recognition to regulatory signaling. Fucosyltransferase 8 (FUT8) is the sole enzyme responsible for core fucosylation, and aberrant fucosylation by dysregulated expression of fucosyltransferases is responsible for the growth of various types of carcinomas. However, the function of FUT8 in the progress of osteosarcoma (OS) has not been reported. In this study, we found that FUT8 is expressed at lower levels in patients with OS and in human OS cell lines such as MNNG/HOS, U2OS, and 143B, suggesting that attenuated expression of FUT8 is involved in the growth and progression of OS. Mechanistically, FUT8 affects the survival strategy of OS by modifying core-fucosylation levels of TNF receptors (TNFRs). Lower fucosylation of TNFRs activates the non-canonical NF-κB signaling pathway, and in turn, decreases mitochondria-dependent apoptosis in OS cells. Together, our results point to FUT8 being a negative regulator of OS that enhances OS-cell apoptosis and suggests a novel therapeutic strategy for treating OS.
糖基化是膜蛋白的一种重要修饰方式，可导致细胞识别到调节信号等多种细胞活动的功能改变。岩藻糖基转移酶 8（FUT8）是唯一负责核心岩藻糖基化的酶，而岩藻糖基转移酶表达失调导致的异常岩藻糖基化是各种类型的癌生长的原因。然而，FUT8 在骨肉瘤（OS）进展中的作用尚未报道。在这项研究中，我们发现 FUT8 在 OS 患者和 MNNG/HOS、U2OS 和 143B 等人类 OS 细胞系中的表达水平较低，这表明 FUT8 的表达减弱参与了 OS 的生长和进展。在机制上，FUT8 通过改变 TNF 受体（TNFRs）的核心岩藻糖基化水平来影响 OS 的存活策略。TNFRs 的低岩藻糖基化激活非经典 NF-κB 信号通路，从而减少 OS 细胞中线粒体依赖的细胞凋亡。总之，我们的结果表明 FUT8 是 OS 的负调控因子，可增强 OS 细胞凋亡，并为治疗 OS 提供了一种新的治疗策略。
