title: Interaction between hypoxia, AKT and HIF-1 signaling in HNSCC and NSCLC: implications for future treatment strategies.
abstract: BACKGROUND
  Hypoxia is a negative prognostic factor and this study investigated the relationship between hypoxia, hypoxia inducible factor 1 (HIF-1) and AKT signaling in head and neck squamous cell carcinoma (HNSCC) and non-small-cell lung cancer (NSCLC).
  pAKT was induced by hypoxia (0.5% O2) in a part of HNSCC (3/4) and squamous (2/3) and adenocarcinoma (1/3) NSCLS lines. AKT-inhibitor MK-2206 reduced hypoxic HIF-1 signaling in most HNSCC cell lines. This reduction did not correlate with hypoxic induction of pAKT or with sensitivity to MK-2206 under hypoxia. Patient biopsies revealed a hypoxia-induced expression pattern of pAKT in HNSCC (n = 16), which was not observed in squamous cell (n = 34) or adenocarcinoma (n = 41) NSCLC.
  
  
  CONCLUSIONS
  The interaction between hypoxia, HIF-1 and AKT signaling varies between tumor types and histologies, which could significantly affect response to targeted therapies.
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Stegeman
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Wenny Jm
authors.initials: WJ
authors.lastname: Peeters
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Marieke Mg
authors.initials: MM
authors.lastname: Verheijen
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery & Department of Medical Biochemistry, Turku University Hospital & University of Turku, Turku, Finland; Department of Otorhinolaryngology-Head & Neck Surgery & Department of Medical Biochemistry, Turku University Hospital & University of Turku, Turku, Finland.
authors.forename: Reidar
authors.initials: R
authors.lastname: Grénman
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Tineke Wh
authors.initials: TW
authors.lastname: Meijer
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Johannes Ham
authors.initials: JH
authors.lastname: Kaanders
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Radiation Oncology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Bussink
keywords: AKT; HIF-1; HNSCC; NSCLC; adenocarcinoma; hypoxia; squamous cell carcinoma