PXD007785 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:40:43.063.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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-09-19 01:50:06 | ID requested | |
1 | 2019-12-18 07:08:43 | announced | |
⏵ 2 | 2024-10-22 04:40:51 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1038/s41598-019-55208-5; |
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] |
Keyword List
curator keyword: Biomedical |
submitter keyword: head and neck cancer, mass spectrometry, signaling pathways, quantitative phosphoproteomics,EGFR-tyrosine kinase inhibitor resistance |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD007785
- Label: PRIDE project
- Name: Genetic aberrations in MAP kinase pathway play an important role in erlotinib resistance in head and neck cancer