Interaction between hypoxia, AKT and HIF-1 signaling in HNSCC and NSCLC: implications for future treatment strategies

Hanneke Stegeman; Paul N Span; Wenny Jm Peeters; Marieke Mg Verheijen; Reidar Grénman; Tineke Wh Meijer; Johannes Ham Kaanders; Johan Bussink

doi:10.4155/fso.15.84

Interaction between hypoxia, AKT and HIF-1 signaling in HNSCC and NSCLC: implications for future treatment strategies

Future Sci OA. 2016 Jan 29;2(1):FSO84. doi: 10.4155/fso.15.84. eCollection 2016 Mar.

Authors

Hanneke Stegeman¹, Paul N Span¹, Wenny Jm Peeters¹, Marieke Mg Verheijen¹, Reidar Grénman², Tineke Wh Meijer¹, Johannes Ham Kaanders¹, Johan Bussink¹

Affiliations

¹ 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.
² 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.

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).

Results/methodology: 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.

Conclusion: The interaction between hypoxia, HIF-1 and AKT signaling varies between tumor types and histologies, which could significantly affect response to targeted therapies.

Keywords: AKT; HIF-1; HNSCC; NSCLC; adenocarcinoma; hypoxia; squamous cell carcinoma.