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.
Highlights
Osteosarcoma (OS) is the most frequent and aggressive primary malignant neoplasm diagnosed in the skeletal system [1]
Reduced expression of core fucosyltransferase Fucosyltransferase 8 (FUT8) in human clinical OS samples and OS cell lines To examine the role of FUT8 in the progression of OS, we first analyzed the expression of FUT8 in clinical samples of normal cancellous bone and OS tissue samples by room temperature (RT)-qPCR
Zhang et al, reported that a glycosyltransferase called N-GalNAc transferase is highly expressed in OS [26]
Summary
Osteosarcoma (OS) is the most frequent and aggressive primary malignant neoplasm diagnosed in the skeletal system [1]. Many patients have to face death threat after diagnosis due to its rapid progression, tendency to metastasize to the lungs, and high recurrence rate [2]. Since the advent of a comprehensive therapeutic strategy in the 1970s, which includes neoadjuvant chemotherapy, surgery, and radiotherapy, the 5-year overall survival rate increased for localized OS [1]. The survival rate has remained unchanged for decades, leaving 30–40% of patients who still cannot benefit from comprehensive therapy [3]. It is important to identify all the factors that contribute to OS progression.
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