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

Radhakrishnan, Aneesha and Nanjappa, Vishalakshi and Raja, Remya and Sathe, Gajanan and Puttamallesh, Vinuth N and Jain, Ankit P and Pinto, Sneha M and Balaji, Sai A and Chavan, Sandip and Sahasrabuddhe, Nandini A and Mathur, Premendu P and Kumar, Mahesh M and Prasad, Keshava TS and Santosh, Vani and Sukumar, Geethanjali and Califano, Joseph A and Rangarajan, Annapoorni and Sidransky, David and Pandey, Akhilesh and Gowda, Harsha and Chatterjee, Aditi (2016) A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma. In: SCIENTIFIC REPORTS, 6 .

PDF Sci_Rep_6_36132_2016.pdf - Published Version Download (2MB)

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.

Item Type:	Journal Article
Publication:	SCIENTIFIC REPORTS
Additional Information:	Copy right for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	03 Dec 2016 10:10
Last Modified:	03 Dec 2016 10:10
URI:	http://eprints.iisc.ac.in/id/eprint/55406

Actions (login required)

View Item