Dataset Information

Dysregulation of splicing proteins in head and neck squamous cell carcinoma

ABSTRACT: Aberrant activation of splicing regulators contributes to oncogenic transformation of cells by modulating the alternative splicing events of key oncogenes. Phosphorylation of splicing factors affects subcellular localization and activity of these proteins. Studies have shown a close association between altered phosphorylation of molecules involved in splicing machinery and cancer. We carried out proteomic and phosphoproteomic analysis of head and neck squamous cell carcinoma (HNSCC) cell lines using tandem mass tag (TMT) labeling approach followed by titanium dioxide-based phosphopeptides enrichment method. LC-MS/MS analysis resulted in the identification of 4,920 phosphosites corresponding to 2,288 proteins in six HNSCC cell lines compared to a normal oral cell line; OKF6/TERT1. Among the proteins identified, 23 kinases were found to be hyperphosphorylated in all HNSCC cell lines compared to the normal oral cell line.

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: PXD001862 | Pride | 2018-10-24

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	HNSCC_TMT_TP_01.raw	Raw
	HNSCC_TMT_TP_longColumn_02.raw	Raw
	HNSCC_TMT_TP_longColumn_03.raw	Raw
	HNSCC_TMT_TP_longColumn_04.raw	Raw
	HNSCC_TMT_TP_longColumn_05.raw	Raw

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Publications

Dysregulation of splicing proteins in head and neck squamous cell carcinoma.

Radhakrishnan Aneesha A Nanjappa Vishalakshi V Raja Remya R Sathe Gajanan G Chavan Sandip S Nirujogi Raja Sekhar RS Patil Arun H AH Solanki Hitendra H Renuse Santosh S Sahasrabuddhe Nandini A NA Mathur Premendu P PP Prasad T S Keshava TS Kumar Prashant P Califano Joseph A JA Sidransky David D Pandey Akhilesh A Gowda Harsha H Chatterjee Aditi A

Cancer biology & therapy 20160206 2

Signaling plays an important role in regulating all cellular pathways. Altered signaling is one of the hallmarks of cancers. Phosphoproteomics enables interrogation of kinase mediated signaling pathways in biological systems. In cancers, this approach can be utilized to identify aberrantly activated pathways that potentially drive proliferation and tumorigenesis. To identify signaling alterations in head and neck squamous cell carcinoma (HNSCC), we carried out proteomic and phosphoproteomic anal ...[more]

PMID: 26853621

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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>