ArticleThe Journal of biological chemistry2012
Epigenetic silencing of the chaperone Cosmc in human leukocytes expressing tn antigen.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 63 citations in OpenAlex.
- From Glycocode to Precision Oncology: Therapeutic Strategies Targeting Aberrant O-GalNAc Glycosylation in Cancer.Chemical reviews · 2026Review
- CD276 immature glycosylation drives colorectal cancer aggressiveness and T cell mediated immune escape.Cell communication and signaling : CCS · 2026Article
- LncSLED1 inhibits monosodium urate-induced macrophage inflammation by promoting Cosmc methylation to upregulate CA72-4.Central-European journal of immunology · 2026Article
- A Comprehensive Analysis of Tn and STn Antigen Expression in Esophageal Adenocarcinoma.Cancers · 2024Article
- Targeting Solid Cancers with a Cancer-Specific Monoclonal Antibody to Surface Expressed Aberrantly O-glycosylated Proteins.Molecular cancer therapeutics · 2023Article
- Review
- Emerging Roles of the Unique Molecular Chaperone Cosmc in the Regulation of Health and Disease.Biomolecules · 2022Review
- Review
- C1GALT1 in health and disease.Oncology letters · 2021Review
- Epigenetic Regulation of Glycosylation in Cancer and Other Diseases.International journal of molecular sciences · 2021Review
- Intestinal epithelial glycosylation in homeostasis and gut microbiota interactions in IBD.Nature reviews. Gastroenterology & hepatology · 2020Review
- Overexpression of Cosmc suppresses cell migration and invasion in different subtypes of breast cancer cells via Tn and T glycans.Bioscience reports · 2020Article
- Development of smart anti-glycan reagents using immunized lampreys.Communications biology · 2020Article
- Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens.Cancer management and research · 2020Article
- DifferentialFrontiers in oncology · 2020Article
- Cosmc Disruption-Mediated Aberrant O-glycosylation Suppresses Breast Cancer Cell Growth via Impairment of CD44.Cancer management and research · 2020Article
- Cosmc overexpression enhances malignancies in human colon cancer.Journal of cellular and molecular medicine · 2020Article
- Multiple cancer-specific antigens are targeted by a chimeric antigen receptor on a single cancer cell.JCI insight · 2019Article
- "Stuck on sugars - how carbohydrates regulate cell adhesion, recognition, and signaling".Glycoconjugate journal · 2019Article
- Representing glycophenotypes: semantic unification of glycobiology resources for disease discovery.Database : the journal of biological databases and curation · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Cosmc is the specific molecular chaperone in the endoplasmic reticulum for T-synthase, a Golgi β3-galactosyltransferase that generates the core 1 O-glycan, Galβ1-3GalNAcα-Ser/Thr, in glycoproteins. Dysfunctional Cosmc results in the formation of inactive T-synthase and consequent expression of the Tn antigen (GalNAcα1-Ser/Thr), which is associated with several human diseases. However, the molecular regulation of expression of Cosmc, which is encoded by a single gene on Xq24, is poorly understood. Here we show that epigenetic silencing of Cosmc through hypermethylation of its promoter leads to loss of Cosmc transcripts in Tn4 cells, an immortalized B cell line from a male patient with a Tn-syndrome-like phenotype. These cells lack T-synthase activity and express the Tn antigen. Treatment of cells with 5-aza-2'-deoxycytidine causes restoration of Cosmc transcripts, restores T-synthase activity, and reduces Tn antigen expression. Bisulfite sequencing shows that CG dinucleotides in the Cosmc core promoter are hypermethylated. Interestingly, several other X-linked genes associated with glycosylation are not silenced in Tn4 cells, and we observed no correlation of a particular DNA methyltransferase to aberrant methylation of Cosmc in these cells. Thus, hypermethylation of the Cosmc promoter in Tn4 cells is relatively specific. Epigenetic silencing of Cosmc provides another mechanism underlying the abnormal expression of the Tn antigen, which may be important in understanding aberrant Tn antigen expression in human diseases, including IgA nephropathy and cancer.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.