PXD007785

PXD007785 is an original dataset announced via ProteomeXchange.

Title	Genetic aberrations in MAP kinase pathway play an important role in erlotinib resistance in head and neck cancer
Description	Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase is overexpressed in 90% of Head and neck squamous cell carcinoma (HNSCC) patients. Clinical trials with EGFR-targeted tyrosine kinase inhibitors such as erlotinib have shown a modest activity in HNSCC alternate mechanisms of resistance are acquired. To investigate these acquired mechanisms of resistance and identify novel therapeutic targets we employed whole exome sequencing of an isogenic pair of erlotinib sensitive (SCC-S) and resistant (SCC-R) HNSCC cell line. We observed single nucleotide variations and copy number alterations in genes related to RAS-RAF-MEK-ERK pathway. To assess the effects of these variations on cellular kinome and we employed SILAC-based phosphoproteomic analysis of SCC-S and SCC-R cell lines. Quantitative phosphoprotein profiling led to identification of 5558 unique phosphopeptides and 5025 unique phosphosites corresponding to 2344 proteins. We observed, 903 phosphopeptides belonging to 579 proteins and 518 phosphopeptides belonging to 368 proteins to be hyper and hypophosphorylated (≥2 fold) in SCC-R cells, respectively. Bioinformatics analysis of differentially phosphorylated proteins showed enrichment of proteins involved in MAPK pathway downstream of EGFR. We identified and validated activation of proteins related to MAPK pathway and its downstream targets in SCC-R cells. We further demonstrated that MAP2K1 inhibitor can be used as an alternative to erlotinib in HNSCC.
HostingRepository	PRIDE
AnnounceDate	2019-12-18
AnnouncementXML	Submission_2019-12-18_07:08:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harsha Gowda
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; isotope labeled residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-19 01:50:06	ID requested
⏵ 1	2019-12-18 07:08:43	announced

Jain AP, Patel K, Pinto S, Radhakrishnan A, Nanjappa V, Kumar M, Raja R, Patil AH, Kumari A, Manoharan M, Karunakaran C, Murugan S, Keshava Prasad TS, Chang X, Mathur PP, Kumar P, Gupta R, Gupta R, Khanna-Gupta A, Sidransky D, Chatterjee A, Gowda H, MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma. Sci Rep, 9(1):18793(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: EGFR-tyrosine kinase inhibitor resistance, signaling pathways, mass spectrometry, quantitative phosphoproteomics, head and neck cancer

Harsha Gowda
contact affiliation	Institute of Bioinformatics , International Technology Park, Bangalore, India
contact email	harsha@ibioinformatics.org
lab head
Harsha Gowda
contact affiliation	Institute of Bioinformatics
contact email	harsha@ibioinformatics.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/12/PXD007785

PRIDE project URI

• PRIDE
  1. PXD007785
     1. Label: PRIDE project
     2. Name: Genetic aberrations in MAP kinase pathway play an important role in erlotinib resistance in head and neck cancer