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

610 Mice, Nude Apoptosis Protein Serine-Threonine Kinases Article Cell Line Mice 03 medical and health sciences name=General Cell Movement /dk/atira/pure/subjectarea/asjc/1000 Animals Humans Phosphorylation Phosphotyrosine 0303 health sciences Oral cancer Forkhead Box Protein O3 Protein-Tyrosine Kinases Immunohistochemistry Caspase 9 3. Good health Harmine Head and Neck Neoplasms Carcinoma, Squamous Cell Female RNA Interference Proto-Oncogene Proteins c-akt Biomarkers
DOI: 10.1038/srep36132 Publication Date: 2016-10-31T10:51:20Z
ABSTRACT
AbstractDespite 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.
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