ArticleBritish journal of cancer2017
Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.
Article in British journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 70 citations in OpenAlex.
- Exploring promising biomarkers based on pathogenic mechanisms in interstitial cystitis/bladder pain syndrome.Nature reviews. Urology · 2026Review
- Enzyme cascade-induced optical sensing of hyaluronidase using an ultraviolet-modified liquid crystal interface.Mikrochimica acta · 2025Article
- Article
- Impact of Hyaluronic Acid on the Cutaneous T-Cell Lymphoma Microenvironment: A Novel Anti-Tumor Mechanism of Bexarotene.Cancers · 2025Article
- Inverted Pyramid Nanostructures Coupled with a Sandwich Immunoassay for SERS Biomarker Detection.Nanomaterials (Basel, Switzerland) · 2025Article
- Deciphering molecular pathways driving cancer invasion and metastasis: advances and therapeutic prospects.Frontiers in oncology · 2025Review
- Review
- CD44 in Bladder Cancer.Cancers · 2024Review
- Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention.iScience · 2024Article
- Teaching an Old Drug a New Trick: Targeting Treatment Resistance in Genitourinary Cancers.Journal of cellular signaling · 2024Article
- Targeting hyaluronic acid synthase-3 (HAS3) for the treatment of advanced renal cell carcinoma.Cancer cell international · 2022Article
- Article
- Hyaluronic acid restored protein permeability across injured human lung microvascular endothelial cells.FASEB bioAdvances · 2022Article
- HMMR promotes peritoneal implantation of gastric cancer by increasing cell-cell interactions.Discover oncology · 2022Article
- Review
- Methods for isolating and analyzing physiological hyaluronan: a review.American journal of physiology. Cell physiology · 2022Review
- The role of RHAMM in cancer: Exposing novel therapeutic vulnerabilities.Frontiers in oncology · 2022Review
- Antitumor effect of 4MU on glioblastoma cells is mediated by senescence induction and CD44, RHAMM and p-ERK modulation.Cell death discovery · 2021Article
- Article
- Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundMolecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets.
methodsData from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules - HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models.
resultsIn clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial-mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with β-catenin, Twist and Snail expression, but negatively with E-cadherin expression.
conclusionsThis study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.
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