Dataset Information

DYRK1A, a potential therapeutic target for head and neck squamous cell carcinoma

ABSTRACT: To identify the activated tyrosine kinase signaling pathways in HNSCC, we carried out phosphotyrosine profiling using a panel of HNSCC cell lines compared to a normal oral keratinocyte. A total of 61 unique phosphosites were identified across these cell lines. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Y321 in all the HNSCC cell lines compared to the normal oral cell line OKF6/TERT1. Inhibition of DYRK1A using its specific siRNA and inhibitor resulted in a decrease in the invasion and colony formation ability of the HNSCC cell lines. Further, the treatment of mice bearing HNSCC xenograft tumors with DYRK1A inhibitor (harmine) showed regression of tumor growth. Our results demonstrate that DYRK1A could be a novel therapeutic target in HNSCC.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Head And Neck Squamous Cell Carcinoma Cell Line

DISEASE(S): Head And Neck Squamous Cell Carcinoma

SUBMITTER: Akhilesh Pandey

LAB HEAD: Akhilesh Pandey

PROVIDER: PXD002132 | Pride | 2018-10-24

REPOSITORIES: Pride

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Publications

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

Radhakrishnan Aneesha A Nanjappa Vishalakshi V Raja Remya R Sathe Gajanan G Puttamallesh Vinuth N VN Jain Ankit P AP Pinto Sneha M SM Balaji Sai A SA Chavan Sandip S Sahasrabuddhe Nandini A NA Mathur Premendu P PP Kumar Mahesh M MM Prasad T S Keshava TS Santosh Vani V Sukumar Geethanjali G Califano Joseph A JA Rangarajan Annapoorni A Sidransky David D Pandey Akhilesh A Gowda Harsha H Chatterjee Aditi A

Scientific reports 20161031

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 tyr ...[more]

PMID: 27796319

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Project description:Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer by incidence worldwide(1). Various chemical carcinogens (tobacco, alcohol and betel nut), human papillomavirus (HPV) infection, and genetic predisposition contribute to the etiology of HNSCC, and to the complex genetic alterations in tumor subsets that differ in prognosis and response to therapies (2). Recently, a comprehensive landscape of genomic and transcriptomic alterations in HNSCC tumors has emerged from The Cancer Genome Atlas (TCGA) Network (3). TCGA revealed novel and previously recognized gene and chromosomal region copy number alterations (CNAs), mutations, and expression clusters, and defined their frequency, co-occurrence, and relationship to common and rare subtypes of HPV(-) and (+) tumors that vary in prognosis. To identify cell line models for determining the functional role and therapeutic importance of these alterations, we are performing whole exome and RNA sequencing and bioinformatic analysis of an expanded panel of 15 HPV(-) and 11 HPV(+) HNSCC cell lines and primary oral keratinocytes. We find that the recurrent genomic alterations in cell lines are remarkably consistent with those found in more aggressive tumors, from which cell lines have traditionally been most readily adapted to culture (4). Genome-wide correlation of CN (copy number) with expression identified a suite of potential drivers or modifier genes that differ by HPV status, and are of potential biologic and therapeutic relevance. Further, our findings elucidate and validate genomic alterations underpinning numerous discoveries made with these widely-used and recently derived HNSCC lines, and provide a roadmap for their potential use as models for future studies of tumor subtypes with worse prognosis. References <ol> <li>Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108.</li> <li>Van Waes C, Musbahi O. Genomics and advances towards precision medicine for head and neck squamous cell carcinoma. Laryngoscope Investig Otolaryngol. 2017;2(5):310-9.</li> <li>Cancer Genome Atlas N. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576-82.</li> <li>White JS, Weissfeld JL, Ragin CC, Rossie KM, Martin CL, Shuster M, et al. The influence of clinical and demographic risk factors on the establishment of head and neck squamous cell carcinoma cell lines. Oral Oncol. 2007;43(7):701-12.</li> </ol>

Dataset Information

DYRK1A, a potential therapeutic target for head and neck squamous cell carcinoma

Publications

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

Similar Datasets

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