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Sci Rep. 2016 Oct 31;6:36132. doi: 10.1038/srep36132.

A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma.

Author information

1
Institute of Bioinformatics, International Technology Park, Bangalore, 560 066, India.
2
Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry 605014, India.
3
Amrita School of Biotechnology, Amrita University, Kollam 690 525, India.
4
Manipal University, Madhav Nagar, Manipal 576104, India.
5
School of Biotechnology, KIIT University, Bhubaneswar 751024, India.
6
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.
7
Department of Neuro-Virology, National Institute of Mental Health and Neurosciences, Bangalore 560029, India.
8
YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore 575018, India.
9
Department of Pathology, National Institute of Mental Health and Neurosciences, Bangalore 560029, India.
10
Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, MD 21204, USA.
11
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
12
McKusick-Nathans Institute of Genetic Medicine,Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
13
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
14
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
15
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers. To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines. Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines. Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth. Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 97.5% (39/40) of HNSCC tissues analyzed. Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC.

PMID:
27796319
PMCID:
PMC5086852
DOI:
10.1038/srep36132
[Indexed for MEDLINE]
Free PMC Article

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