Role of cancer stem-cell marker doublecortin-like kinase 1 in head and neck squamous cell carcinoma

Lorenz Kadletz; Dietmar Thurnher; Robert Wiebringhaus; Boban M Erovic; Ulana Kotowski; Sven Schneider; Rainer Schmid; Lukas Kenner; Gregor Heiduschka

doi:10.1016/j.oraloncology.2017.02.007

Role of cancer stem-cell marker doublecortin-like kinase 1 in head and neck squamous cell carcinoma

Oral Oncol. 2017 Apr:67:109-118. doi: 10.1016/j.oraloncology.2017.02.007. Epub 2017 Feb 27.

Authors

Lorenz Kadletz¹, Dietmar Thurnher², Robert Wiebringhaus³, Boban M Erovic¹, Ulana Kotowski¹, Sven Schneider¹, Rainer Schmid⁴, Lukas Kenner⁵, Gregor Heiduschka⁶

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
² Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Graz, Graz, Austria.
³ Department of Pathology, Medical University of Vienna, Vienna, Austria.
⁴ Department of Radiotherapy and - Oncology, Medical University of Vienna, Austria.
⁵ Department of Pathology, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria; Institute of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria.
⁶ Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria. Electronic address: gregor.heiduschka@meduniwien.ac.at.

PMID: 28351564
DOI: 10.1016/j.oraloncology.2017.02.007

Abstract

Background: So far, no data is available on the role of the tumor stem cell marker doublecortin-like kinase 1 (DCLK1) in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate DCLK1 expression in HNSCC patients that underwent surgery and postoperative radiotherapy, and to assess its potential as a therapeutic target in vitro.

Methods: We immunohistochemically stained for DCLK1 in 127 sections of HNSCC samples obtained during surgery of HNSCC patients and correlated the expression to patients' overall- and disease-free survival, as well as human papilloma virus (HPV) status. Additionally, we compared our survival data with data obtained from The Cancer Genome Atlas (TCGA). The effects of the DCLK1 inhibitor LRRK-2-in-1 on HNSCC cell lines alone and in combination with irradiation.

Results: Expression of DCLK1 in 127 patients was associated with poor survival. In particular, DCLK1 expression had a significant impact on survival of oropharyngeal carcinoma patients. Specifically, DCLK1⁺/HPV^- patients had the worst prognosis after simultaneous assessment of DCLK1 and HPV status in comparison to the other three possible DCLK1/HPV constellations. Higher levels of DCLK1 mRNA were also associated with poor clinical outcome. Inhibition of DCLK1 in our HNSCC cell lines led to growth arrest and induction of apoptosis. The combination of DCLK1 inhibition with irradiation had a synergistic effect.

Conclusion: Firstly, DCLK1 is a prognostic biomarker for shortened survival. Secondly, through inhibition of DCLK1, it may serve as a therapeutic target as well.

Keywords: DCLK1; HPV; Head and neck; LRRK-2-in-1; Radiotherapy; Squamous cell carcinoma.

MeSH terms

Carcinoma, Squamous Cell / metabolism*
Doublecortin Domain Proteins
Female
Head and Neck Neoplasms / metabolism*
Humans
Male
Microtubule-Associated Proteins / metabolism*
Neoplastic Stem Cells / metabolism*
Neuropeptides / metabolism*
Squamous Cell Carcinoma of Head and Neck

Substances

Doublecortin Domain Proteins
Microtubule-Associated Proteins
Neuropeptides