1. Alpha-(1,6)-fucosyltransferase (FUT8) affects the survival strategy of osteosarcoma by remodeling TNF/NF-κB2 signaling
- Author
-
Ting Yuan, Lenian Zhou, Yang Dong, Shanyi Lin, Quanjun Yang, Shumin Zhou, Hanqiang Jin, and Qingcheng Yang
- Subjects
Cancer Research ,Fucosyltransferase ,Immunology ,Glycobiology ,Mice, Nude ,Apoptosis ,Article ,Cellular and Molecular Neuroscience ,Mice ,NF-kappa B p52 Subunit ,Bone cancer ,Animals ,Humans ,Receptor ,Fucosylation ,Osteosarcoma ,biology ,QH573-671 ,Chemistry ,Cell Biology ,Fucosyltransferases ,Survival Analysis ,Membrane protein ,Cell culture ,biology.protein ,Cancer research ,Tumor necrosis factor alpha ,Female ,Signal transduction ,Cytology ,Signal Transduction - Abstract
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.
- Published
- 2021