ArticleOncogene2022
Reduction in O-glycome induces differentially glycosylated CD44 to promote stemness and metastasis in pancreatic cancer.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Encoding Cell-Surface Receptor Function Through Glycosylation: Lessons From CD44.Chembiochem : a European journal of chemical biology · 2026Review
- Distinct glycosyltransferase expression governs organ-specific survival in pancreatic cancer metastasis.Oncogene · 2026Article
- Spheroid cultures reveal cancer stem cell enrichment and distinct chemotherapeutic response in triple-negative breast cancer.BMC cancer · 2026Article
- Post-Translational Modifications in Pancreatic Cancer: Mechanisms to Clinical Applications.Journal of gastroenterology and hepatology · 2026Review
- Integrative Analysis of Glycosylation-Related Genes Reveals Prognostic Subtypes, Immune Evasion, and Therapeutic Vulnerabilities in Lung Adenocarcinoma.Oncology research · 2026Article
- Cisplatin-mediated activation of NF-κB promotes lung cancer stem cell formation via DNA repair pathways.Journal of translational medicine · 2025Article
- CD44 as a Central Integrator of Inflammation and Fibrosis: From Molecular Signaling to Environmental Modulation.International journal of molecular sciences · 2025Review
- Sugar symphony: glycosylation in cancer metabolism and stemness.Trends in cell biology · 2025Review
- C1GALT1 expression predicts poor survival in osteosarcoma and is crucial for ABCC1 transporter-mediated doxorubicin resistance.The Journal of pathology · 2025Article
- Targeting protein modification: a new direction for immunotherapy of pancreatic cancer.International journal of biological sciences · 2025Review
- Aberrations in the glycosylation of receptor tyrosine kinases: A focus on lung adenocarcinoma.CytoJournal · 2025Review
- Glycosylation in Cancer.Handbook of experimental pharmacology · 2025Review
- B3GNT5 is a novel marker correlated with malignant phenotype and poor outcome in pancreatic cancer.iScience · 2024Article
- The role of gastric mucins and mucin-related glycans in gastric cancers.Cancer science · 2024Review
- Impaired Glycosylation of Gastric Mucins Drives Gastric Tumorigenesis and Serves as a Novel Therapeutic Target.Gastroenterology · 2024Article
- Review
- CD44 and its implication in neoplastic diseases.MedComm · 2024Review
- Article
- Truncation of GalNAc-type O-glycans Suppresses CD44-mediated Osteoclastogenesis and Bone Metastasis in Breast Cancer.Molecular cancer research : MCR · 2023Article
- Altered Glycosylation in Progression and Management of Bladder Cancer.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Aberrant protein glycosylation has been shown to have a significant contribution in aggressive cancer, including pancreatic cancer (PC). Emerging evidence has implicated the involvement of cancer stem cells (CSCs) in PC aggressiveness; however, the contribution of glycosylation on self-renewal properties and maintenance of CSC is understudied. Here, using several in vitro and in vivo models lacking C1GALT1 expression, we identified the role of aberrant O-glycosylation in stemness properties and aggressive PC metastasis. A loss in C1GALT1 was found to result in the truncation of O-glycosylation on several glycoproteins with an enrichment of Tn carbohydrate antigen. Mapping of Tn-bearing glycoproteins in C1GALT1 KO cells identified significant Tn enrichment on CSC glycoprotein CD44. Notably, a loss of C1GALT1 in PC cells was found to enhance CSC features (side population-SP, ALDH1+, and tumorspheres) and self-renewal markers NANOG, SOX9, and KLF4. Furthermore, a loss of CD44 in existing C1GALT1 KO cells decreased NANOG expression and CSC features. We determined that O-glycosylation of CD44 activates ERK/NF-kB signaling, which results in increased NANOG expression in PC cells that facilitated the alteration of CSC features, suggesting that NANOG is essential for PC stemness. Finally, we identified that loss of C1GALT1 expression was found to augment tumorigenic and metastatic potential, while an additional loss of CD44 in these cells reversed the effects. Overall, our results identified that truncation of O-glycans on CD44 increases NANOG activation that mediates increased CSC activation.
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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.