ArticleScientific reports2018
NFκB activation in differentiating glioblastoma stem-like cells is promoted by hyaluronic acid signaling through TLR4.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Tumor-intrinsic TLR4 signaling as a context-dependent rheostat in glioblastoma.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Design of a novel multiepitope vaccine against glioblastoma by in silico approaches.Scientific reports · 2025Article
- Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025Review
- Article
- Effects of Hyaluronan on Breast Cancer Aggressiveness.Cancers · 2023Review
- Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments.Molecular cancer · 2023Review
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma.Journal of hematology & oncology · 2021Review
- Inflammation, Extracellular Matrix Remodeling, and Proteostasis in Tumor Microenvironment.International journal of molecular sciences · 2021Review
- Review
- ADO/hypotaurine: a novel metabolic pathway contributing to glioblastoma development.Cell death discovery · 2021Article
- Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes.Scientific reports · 2021Article
- Review
- Article
- Dissecting and rebuilding the glioblastoma microenvironment with engineered materials.Nature reviews. Materials · 2019Article
- Article
- Melatonin promotes neuroblastoma cell differentiation by activating hyaluronan synthase 3-induced mitophagy.Cancer medicine · 2019Article
- Molecular and Clinical Insights into the Invasive Capacity of Glioblastoma Cells.Journal of oncology · 2019Review
- BioNetStat: A Tool for Biological Networks Differential Analysis.Frontiers in genetics · 2019Article
- Genome-wide expression profiling of glioblastoma using a large combined cohort.Scientific reports · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously described that the NFκB pathway is upregulated during differentiation of glioblastoma stem-like cells (GSCs) which keeps differentiating GSCs in a proliferative astrocytic precursor state. However, extracellular signals and cellular mediators of this pathway are not clear yet. Here, we show that TLR4 is a key factor to promote NFκB activation in differentiating GSCs. TLR4 is upregulated during differentiation of GSCs and promotes transcriptional activation of NFκB as determined by luciferase-reporter assays and expression of NFκB target genes. Downregulation of TLR4 by shRNAs or blockade with anti-TLR4 specific antibodies drastically inhibited NFκB activity which promoted further differentiation and reduced proliferation of GSCs. We found that hyaluronic acid (HA), a main component of brain extracellular matrix, triggers the TLR4-NFκB pathway in differentiating GSCs. Moreover, HA is synthesized and released by GSCs undergoing differentiation and leads to transcriptional activation of NFκB, which is inhibited following downregulation of TLR4 or blockade of HA synthesis. Thus, we have demonstrated that during the process of differentiation, GSCs upregulate TLR4 and release the TLR4 ligand HA, which activates the TLR4-NFκB signaling pathway. This strategy may efficiently be used by differentiating GSCs to maintain their proliferative potential and consequently their tumorigenic capacity.
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