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Hypoxia-inducible factor-1alpha activation in HPV-positive head and neck squamous cell carcinoma cell lines

Knuth, Jennifer ; Sharma, Shachi J. ; W├╝rdemann, Nora ; Holler, Claudia ; Garvalov, Boyan K. ; Acker, Till ; Wittekindt, Claus ; Wagner, Steffen ; Klussmann, Jens P.


Originalveröffentlichung: (2017) Oncotarget 8:89681-89691 doi: 10.18632/oncotarget.20813
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URN: urn:nbn:de:hebis:26-opus-157532
URL: http://geb.uni-giessen.de/geb/volltexte/2020/15753/


Sammlung: Open Access - Publikationsfonds
Universität Justus-Liebig-Universit├Ąt Gie├čen
Institut: Department of Otorhinolaryngology, Head and Neck Surgery
Fachgebiet: Medizin
DDC-Sachgruppe: Medizin
Dokumentart: Aufsatz
Sprache: Englisch
Erstellungsjahr: 2017
Publikationsdatum: 01.12.2020
Kurzfassung auf Englisch: Purpose: 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.
Lizenz: Lizenz-Logo  Creative Commons - Namensnennung