PXD007769

PXD007769 is an original dataset announced via ProteomeXchange.

Title	SILAC-based quantitative tyrosine phosphoproteomic profiling identifies alternative therapeutic targets to erlotinib in head and neck squamous cell carcinoma
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 SILAC-based tyrosine phosphoteomic analysis of an isogenic pair of erlotinib sensitive (SCC-S) and resistant (SCC-R) HNSCC cell line. Quantitative phosphotyrosine profiling revealed 98 phosphopeptides belonging to 64 proteins and 66 phosphopeptides belonging to 52 proteins to be hyper and hypophosphorylated (≥2 fold) in SCC-R cells, respectively. Several proteins such MET proto-oncogene, receptor tyrosine kinase (MET) and CRK like proto-oncogene, adaptor protein (CRKL) known to mediate erlotinib resistance in HNSCC and lung cancer were found to be dysregulated. Bioinformatics analysis of differentially phosphorylated proteins showed enrichment of proteins involved in focal adhesion kinase (FAK) pathway downstream of EGFR. We identified and validated activation of several phosphorylation sites of protein tyrosine kinase 2 (PTK2) in SCC-R cells and its downstream targets. We further demonstrated that CUB-domain containing protein 1 (CDCP1), an upstream regulator of PTK2 activity and PTK2 can be targeted in combination as an alternative to erlotinib in HNSCC.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:07:27.077.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	2017-09-18 03:44:26	ID requested
1	2022-10-13 02:51:28	announced
⏵ 2	2023-11-14 07:07:27	announced	2023-11-14: Updated project metadata.

Jain AP, Radhakrishnan A, Pinto S, Patel K, Kumar M, Nanjappa V, Raja R, Keshava Prasad TS, Mathur PP, Sidransky D, Chatterjee A, Gowda H, How to Achieve Therapeutic Response in Erlotinib-Resistant Head and Neck Squamous Cell Carcinoma? New Insights from Stable Isotope Labeling with Amino Acids in Cell Culture-Based Quantitative Tyrosine Phosphoproteomics. OMICS, 25(9):605-616(2021) [pubmed]

curator keyword: Biomedical

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

Harsha Gowda
contact affiliation	Institute of Bioinformatics , International Technology Park, Bangalore, India.
contact email	harsha@ibioinformatics.org
lab head
Harsha Gowda
contact affiliation	QIMR Berghofer Medical Research Institute
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/2022/10/PXD007769

PRIDE project URI

• PRIDE
  1. PXD007769
     1. Label: PRIDE project
     2. Name: SILAC-based quantitative tyrosine phosphoproteomic profiling identifies alternative therapeutic targets to erlotinib in head and neck squamous cell carcinoma