ArticleOncotarget2016
Heparan sulfate hexasaccharide selectively inhibits cancer stem cells self-renewal by activating p38 MAP kinase.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- New Hope for Pancreatic Ductal Adenocarcinoma Treatment Targeting Endoplasmic Reticulum Stress Response: A Systematic Review.International journal of molecular sciences · 2018Pooled it
- The Role of Papaverine in the Molecular and Biomechanical Mechanisms of Cervical Ripening: A Narrative Review.International journal of molecular sciences · 2026Review
- Review
- Heparin, Heparin-like Molecules, and Heparin Mimetics in Breast Cancer: A Concise Review.Biomolecules · 2025Review
- MAPK14/p38α shapes the molecular landscape of endometrial cancer and promotes tumorigenic characteristics.Cell reports · 2025Article
- Non-Anticoagulant Activities of Low Molecular Weight Heparins-A Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Designing Synthetic, Sulfated Glycosaminoglycan Mimetics That Are Orally Bioavailable and ExhibitingJournal of medicinal chemistry · 2023Article
- Review
- Glycan Modulation of Insulin-like Growth Factor-1 Receptor.Angewandte Chemie (International ed. in English) · 2022Article
- Role of p38 MAP kinase in cancer stem cells and metastasis.Oncogene · 2022Review
- Pharmacokinetic, Hemostatic, and Anticancer Properties of a Low-Anticoagulant Bovine Heparin.TH open : companion journal to thrombosis and haemostasis · 2022Article
- ING4 Promotes Stemness Enrichment of Human Renal Cell Carcinoma Cells Through Inhibiting DUSP4 Expression to Activate the p38 MAPK/type I IFN-Stimulated Gene Signaling Pathway.Frontiers in pharmacology · 2022Article
- 3-Computational and structural biotechnology journal · 2022Article
- Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.Cancer communications (London, England) · 2021Review
- Combinatorial Virtual Library Screening Study of Transforming Growth Factor-β2-Chondroitin Sulfate System.International journal of molecular sciences · 2021Article
- Enzyme immobilization offers a robust tool to scale up the production of longer, diverse, natural glycosaminoglycan oligosaccharides.Glycobiology · 2020Article
- Rigorous analysis of free solution glycosaminoglycan dynamics using simple, new tools.Glycobiology · 2020Article
- Combinatorial virtual library screening analysis of antithrombin binding oligosaccharide motif generation by heparan sulfate 3-Computational and structural biotechnology journal · 2020Article
- Heparan Sulfate Proteoglycans: Key Mediators of Stem Cell Function.Frontiers in cell and developmental biology · 2020Review
- Structural Insights Into How Proteoglycans Determine Chemokine-CXCR1/CXCR2 Interactions: Progress and Challenges.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Heparan sulfate (HS) plays a role in the majority of essential hallmarks of cancer, yet its ability to modulate self-renewal, especially of cancer stem cells (CSCs), remains unknown. We have discovered that a non-anticoagulant HS hexasaccharide (HS06) sequence, but not other shorter or longer sequences, selectively inhibited CSC self-renewal and induced apoptosis in colorectal, pancreatic, and breast CSCs suggesting a very general phenomenon. HS06 inhibition of CSCs relied upon early and sustained activation of p38α/β mitogen activated protein kinase (MAPK) but not other MAPKs family members i.e. ERK and JNK. In contrast, polymeric HS induced exactly opposite changes in MAPK activation and failed to inhibit CSCs. In fact, TCF4 signaling, a critical regulator of CSC self-renewal, was inhibited by HS06 in a p38 activation dependent fashion. In conclusion, HS06 selectively inhibits CSCs self-renewal by causing isoform specific activation of p38MAPK to inhibit TCF4 signaling. These observations on chain length-induced specificity carry major mechanistic implications with regard to HS in cancer biology, while also presenting a novel paradigm for developing novel anti-CSC hexasaccharides that prevent cancer relapse.Heparan sulfate (HS) of specific length, i.e., hexasaccharide (HS06), but not longer or shorter sequences, selectively inhibit cancer stem cells (CSCs) through isoform specific activation of p38 mitogen-activated protein kinase. These findings will have major implication for developing chemical probes to decipher complex signaling events that govern cancer stem cells. Additionally, there are direct implications for designing glycosaminoglycan based cancer therapies to selectively target CSCs that escape killing by traditional chemotherapy threatening cancer relapse.
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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.