Dataset Information

N-Glycosylation of the Epidermal Growth Factor Receptor (EGFR) Derived from Human Oral Squamous Carcinoma Cells with beta-Catenin/CREB-Binding Protein (CBP) Inhibition

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos, 6550 iFunnel Q-TOF LC/MS, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Oral Squamous Cell Carcinoma,Tongue Squamous Cell Carcinoma,Head And Neck Squamous Cell Carcinoma

SUBMITTER: Kevin Chandler

LAB HEAD: Catherine E Costello

PROVIDER: PXD017060 | Pride | 2020-03-26

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20170512_Cal27_DMSO_EGFR_18O_PNGaseF.raw	Raw
	20170512_Cal27_DMSO_EGFR_18O_control.raw	Raw
	20170512_Cal27_DMSO_EGFR_18O_control_170512164256.raw	Raw
	20170512_Cal27_ICG001_EGFR_18O_PNGaseF.raw	Raw
	20170512_Cal27_ICG001_EGFR_18O_control.raw	Raw

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Publications

β-Catenin/CBP inhibition alters epidermal growth factor receptor fucosylation status in oral squamous cell carcinoma.

Chandler Kevin Brown KB Alamoud Khalid A KA Stahl Vanessa L VL Nguyen Bach-Cuc BC Kartha Vinay K VK Bais Manish V MV Nomoto Kenichi K Owa Takashi T Monti Stefano S Kukuruzinska Maria A MA Costello Catherine E CE

Molecular omics 20200323 3

Epidermal growth factor receptor (EGFR) is a major driver of head and neck cancer, a devastating malignancy with a major sub-site in the oral cavity manifesting as oral squamous cell carcinoma (OSCC). EGFR is a glycoprotein receptor tyrosine kinase (RTK) whose activity is upregulated in >80% OSCC. Current anti-EGFR therapy relies on the use of cetuximab, a monoclonal antibody against EGFR, although it has had only a limited response in patients. Here, we uncover a novel mechanism regulating EGFR ...[more]

PMID: 32203567

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