Knuth, JenniferJenniferKnuthSharma, Shachi J.Shachi J.SharmaWürdemann, NoraNoraWürdemannHoller, ClaudiaClaudiaHollerGarvalov, Boyan K.Boyan K.GarvalovAcker, TillTillAckerWittekindt, ClausClausWittekindtWagner, SteffenSteffenWagnerKlussmann, Jens P.Jens P.Klussmann2022-11-182020-12-012022-11-182017http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-157532https://jlupub.ub.uni-giessen.de/handle/jlupub/9605http://dx.doi.org/10.22029/jlupub-8993Purpose: Human papillomavirus (HPV) is a causative agent for a rising number of head and neck squamous cell carcinomas (HNSCC), which are characterized by distinct tumor biology. Hypoxia inducible-factor (HIF) signaling influences initiation and progression of carcinogenesis and HPV oncoproteins have evolved to highjack cellular pathways for viral reproduction. Therefore, we investigated whether HPV activates HIF-1alpha expression in HNSCC.Experimental Technique: HPV-positive and -negative HNSCC cells were examined for adaptive responses to hypoxia. Expression of HIF-1alpha, prolyl hydroxylasedomain protein 2 (PHD2) and E-cadherin was analyzed by Western blotting, immunofluorescence (IF) microscopy and migration/wound healing assays.Results: HPV-positive HNSCC cells showed higher HIF-1alpha and PHD2 protein levels under normoxia and hypoxia. HIF-1alpha hydroxylation was reduced in HPV-positive HNSCC cell lines under PHD and proteasomal inhibition. In vitro wound healing assays showed impairment of migration and proliferation by HIF-1alpha pathway activation in HPV-negative cell lines only. In contrast, migration and proliferation in HPV-positive cell lines was impaired by HIF-1alpha specific siRNA.Conclusions: HPV-positive HNSCC cells show activation of the HIF pathway and adaptation to HIF-1alpha upregulation, representing potential therapeutic targets in this emerging tumor entity.enNamensnennung 3.0 Internationalhuman papillomavirus (hpv)head and neck squamous cell carcinoma (hnscc)hypoxiahypoxia inducible factor-1alpa (hif-1alpha)ddc:610