PXD017060-1

PXD017060 is an original dataset announced via ProteomeXchange.

Title	N-Glycosylation of the Epidermal Growth Factor Receptor (EGFR) Derived from Human Oral Squamous Carcinoma Cells with beta-Catenin/CREB-Binding Protein (CBP) Inhibition
Description	Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in the world; oral squamous cell carcinomas (OSCC) account for the majority of HNSCC cases. A major driver of OSCC is the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK) with 12 N-glycosylation sites whose activity is aberrantly upregulated in 80-90% of tumors. EGFR antennary-fucosylated glycans have been shown to suppress EGFR dimerization and signaling in lung adenocarcinoma. High levels of fucosylated glycan epitopes have also been observed in OSCC, but invasive regions lose expression of linkage-specific fucosylated epitopes, suggesting that certain fucosylated glycans are involved in the suppression of cell growth and invasion. We found that EGFR from metastatic HSC-3 cells has low levels of fucosylated N-glycans, while EGFR from non-metastatic CAL27 cells shows higher levels of fucosylation at multiple EGFR glycosylation sites including sites N420 and N579, via nUPLC-MS/MS. In cell culture and in mouse tumor xenografts, treatment with ICG-001, a small molecule inhibitor of the interaction between nuclear -catenin and CREB-binding protein (CBP) resulted in higher expression of FUT2 and FUT3, higher fucosylation of EGFR at sites N420 and N579, and decreased EGFR abundance. In addition, we have performed in-depth characterization of multiply-fucosylated N-glycans via glycopeptide tandem mass spectrometry to understand which fucosylated glycan epitopes are involved in the observed effect.
HostingRepository	PRIDE
AnnounceDate	2020-03-26
AnnouncementXML	Submission_2020-03-26_02:41:03.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kevin Chandler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; 6550 iFunnel Q-TOF LC/MS; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-10 03:58:46	ID requested
⏵ 1	2020-03-26 02:41:04	announced

Chandler KB, Alamoud KA, Stahl VL, Nguyen BC, Kartha VK, Bais MV, Nomoto K, Owa T, Monti S, Kukuruzinska MA, Costello CE, -Catenin/CBP inhibition alters epidermal growth factor receptor fucosylation status in oral squamous cell carcinoma. Mol Omics, 16(3):195-209(2020) [pubmed]

submitter keyword: Human, LC-MS/MS, EGFR, epidermal growth factor receptor, OSCC, oral squamous cell carcinoma, head and neck cancer, CAL27, HSC-3, beta-catenin/CBP inhibition, CREB-binding protein, glycopeptide, glycoproteomics

Catherine E Costello
contact affiliation	Center for Biomedical Mass Spectrometry Boston University School of Medicine 670 Albany St, Rm 511 Boston, MA 02118-2646 USA
contact email	cecmsms@bu.edu
lab head
Kevin Chandler
contact affiliation	Boston University School of Medicine
contact email	chandler64@gmail.com
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/2020/03/PXD017060

PRIDE project URI

• PRIDE
  1. PXD017060
     1. Label: PRIDE project
     2. Name: N-Glycosylation of the Epidermal Growth Factor Receptor (EGFR) Derived from Human Oral Squamous Carcinoma Cells with beta-Catenin/CREB-Binding Protein (CBP) Inhibition