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

DYRK1A
DOI: 10.1038/srep36132 Publication Date: 2016-10-31T10:51:20Z
ABSTRACT
Despite advances in clinical management, 5-year survival rate 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 most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority total phosphorylation, it is critical activation signaling pathways plays significant role driving cancers. To identify activated kinase HNSCC, we compared phosphotyrosine profiles panel HNSCC lines normal oral keratinocyte line. Dual-specificity tyrosine-(Y)-phosphorylation regulated 1A (DYRK1A) was kinases hyperphosphorylated at Tyr-321 all lines. Inhibition DYRK1A resulted an increased apoptosis decrease invasion colony formation ability Further, administration small molecular inhibitor against mice bearing xenograft tumors induced regression tumor growth. Immunohistochemical labeling primary tissues using tissue microarrays revealed strong moderate staining 97.5% (39/40) analyzed. Taken together our results suggest that could be novel therapeutic target HNSCC.
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