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• W1965068547 abstract "Abstract High‐risk human papillomavirus ( HPV )‐positive head and neck squamous cell carcinomas ( HNSCC s) are highly invasive; however the identity of downstream effectors responsible for their aggressive phenotype remains underinvestigated. Here, we report that HPV ‐mediated up‐regulation of heparanase enzyme can provide mechanistic explanation for augmented invasiveness of HPV ‐positive HNSCC s. Heparanase is the sole mammalian enzyme (endo‐β‐ d ‐glucuronidase) degrading heparan sulphate glycosaminoglycan, key polysaccharide of the extracellular matrix. Cleavage of heparan sulphate by heparanase leads to disassembly of extracellular barriers, enabling local invasion and metastatic spread of the tumour, and releases heparan sulphate‐bound growth factors from the extracellular depots. Heparanase is tightly implicated in head and neck cancer progression; yet, molecular mechanisms underlying transcriptional activation of the heparanase gene in HNSCC are largely unknown. We found that HPV 16 oncogene E6 is capable of inducing overexpression of heparanase in HNSCC . Notably, radiation treatment dose‐dependently suppresses E6‐induced heparanase expression in vitro . Our results provide the first evidence for a functional involvement of HPV in heparanase induction in head and neck tumourigenesis and, given ongoing clinical testing of several heparanase‐inhibiting compounds, offer important avenue for future therapeutic exploration in HNSCC , as well as other HPV ‐associated malignancies ( i.e . cervical carcinoma)." @default.
• W1965068547 created "2016-06-24" @default.
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• W1965068547 date "2013-11-28" @default.
• W1965068547 modified "2023-10-16" @default.
• W1965068547 title "Induction of heparanase by<scp>HPV</scp>E6 oncogene in head and neck squamous cell carcinoma" @default.
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• W1965068547 doi "https://doi.org/10.1111/jcmm.12179" @default.
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