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

Aneesha Radhakrishnan; Vishalakshi Nanjappa; Remya Raja; Gajanan Sathe; Vinuth N. Puttamallesh; Ankit P. Jain; Sneha M. Pinto; Sai A. Balaji; Sandip Chavan; Nandini A. Sahasrabuddhe; Premendu P. Mathur; Mahesh M. Kumar; T. S.Keshava Prasad; Vani Santosh; Geethanjali Sukumar; Joseph A. Califano; Annapoorni Rangarajan; David Sidransky; Akhilesh Pandey; Harsha Gowda; Aditi Chatterjee

doi:10.1038/srep36132

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

Aneesha Radhakrishnan, Vishalakshi Nanjappa, Remya Raja, Gajanan Sathe, Vinuth N. Puttamallesh, Ankit P. Jain, Sneha M. Pinto, Sai A. Balaji, Sandip Chavan, Nandini A. Sahasrabuddhe, Premendu P. Mathur, Mahesh M. Kumar, T. S.Keshava Prasad, Vani Santosh, Geethanjali Sukumar, Joseph A. Califano, Annapoorni Rangarajan, David Sidransky, Akhilesh Pandey, Harsha GowdaAditi Chatterjee

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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.

Original language	English
Article number	36132
Number of pages	15
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep36132
Publication status	Published - 31 Oct 2016

Keywords

Biomarkers
Oral cancer

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General

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Radhakrishnan, A., Nanjappa, V., Raja, R., Sathe, G., Puttamallesh, V. N., Jain, A. P., Pinto, S. M., Balaji, S. A., Chavan, S., Sahasrabuddhe, N. A., Mathur, P. P., Kumar, M. M., Prasad, T. S. K., Santosh, V., Sukumar, G., Califano, J. A., Rangarajan, A., Sidransky, D., Pandey, A., ... Chatterjee, A. (2016). A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma. Scientific Reports, 6, Article 36132. https://doi.org/10.1038/srep36132

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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.",

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Radhakrishnan, A, Nanjappa, V, Raja, R, Sathe, G, Puttamallesh, VN, Jain, AP, Pinto, SM, Balaji, SA, Chavan, S, Sahasrabuddhe, NA, Mathur, PP, Kumar, MM, Prasad, TSK, Santosh, V, Sukumar, G, Califano, JA, Rangarajan, A, Sidransky, D, Pandey, A, Gowda, H & Chatterjee, A 2016, 'A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma', Scientific Reports, vol. 6, 36132. https://doi.org/10.1038/srep36132

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AU - Radhakrishnan, Aneesha

AU - Nanjappa, Vishalakshi

AU - Raja, Remya

AU - Sathe, Gajanan

AU - Puttamallesh, Vinuth N.

AU - Jain, Ankit P.

AU - Pinto, Sneha M.

AU - Balaji, Sai A.

AU - Chavan, Sandip

AU - Sahasrabuddhe, Nandini A.

AU - Mathur, Premendu P.

AU - Kumar, Mahesh M.

AU - Prasad, T. S.Keshava

AU - Santosh, Vani

AU - Sukumar, Geethanjali

AU - Califano, Joseph A.

AU - Rangarajan, Annapoorni

AU - Sidransky, David

AU - Pandey, Akhilesh

AU - Gowda, Harsha

AU - Chatterjee, Aditi

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N2 - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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