Elevation of nucleocytoplasmic β-N-acetylglucosaminidase (O-GlcNAcase) activity in thyroid cancers

Abstract

Abstract. Single N-acetylglucosamine residues attached by O-linkage to serine or threonine (O-GlcNAc) are an abundant, dynamic and inducible post-translational modification of cytoplasmic and nuclear proteins. This study analyzes the activity of the enzyme involved in the removal of these sugar residues, i.e. ß-N-acetylglucosaminidase (O-GlcNAcase) as well as the level of O-GlcNAc in benign and malignant thyroid lesions. Our results demonstrate increased activity of the enzyme in thyroid cancers in comparison to non-neoplastic lesions and adenomas. O-GlcNAc-modified proteins in thyroid cells have a predominantly nuclear distribution and are more abundant in non-neoplastic lesions than in tumors. Understanding the aberrant O-GlcNAc metabolism in thyroid cancer cells may be helpful for developing new diagnostic or treatment methods.

O-GlcNAcylation enhances anaplastic thyroid carcinoma malignancy

“…Additionally, a previous study proposed OGA activity to be significantly higher and O-GlcNAcylation to be lower in tumor tissue compared with corresponding normal tissue (31). Similarly, a different study demonstrated increased activity of OGA A B activity and decreased O-GlcNAc levels in thyroid cancer compared with benign lesions (16). By contrast, the present study demonstrated that an increase in O-GlcNAcylation was advantageous for the malignancy of ATC cells; however, the two different findings were not mutually contradictory.…”

“…Although it has been proposed that aberrant O-GlcNAc metabolism is associated with the malignant properties of a variety of thyroid cancer cell types, and previous studies have indicated that O-GlcNAcylation participates in the functional regulation of ATC cells by modulating Akt1 activity (16,17), the exact roles of O-GlcNAc in thyroid cancer pathogenesis and progression remain to be established.…”

Down-regulation of β-N-acetyl-D-glucosaminidase increases Akt1 activity in thyroid anaplastic cancer cells

“…Our previous studies concerning O-GlcNAcylation in thyroid lesions demonstrated increased activity of O-GlcNAcase in cancers in comparison to non-neoplastic cells (20). Thus, we expected that an increase in O-GlcNAcylation would be disadvantageous for anaplastic cancer cells.…”

Aberrant O-GlcNAcylated Proteins: New Perspectives in Breast and Colorectal Cancer

“…Enhanced O -GlcNAcylation level corresponding to increased OGT and decreased OGA expression is commonly observed in various cancers including bone (41), bladder (42), breast (26, 43–45), bile duct (46), colon (47–49), leukemia (50), liver (51), lung (47), ovary (36), pancreas (30), and prostate (52, 53). Alteration of this glycosylation in thyroid cancer, however, occurs in the opposite way (54). Interestingly, no mutations in OGT and OGA genes have been reported in human cancers, suggesting that these enzymes are tightly conserved.…”