{"doi":"10.1039/d0mo00009d","title":"β-Catenin/CBP inhibition alters epidermal growth factor receptor fucosylation status in oral squamous cell carcinoma","abstract":"Abstract 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 activity, identifying a role of the nuclear branch of the Wnt/β-catenin signaling pathway, the β-catenin/CBP axis, in control of post-translational modification of N-glycans on the EGFR. Genomic and structural analyses reveal that β-catenin/CBP signaling represses fucosylation on the antennae of N-linked glycans on EGFR. By employing nUPLC-MS/MS, we determined that malignant human OSCC cells harbor EGFR with a paucity of N-glycan antennary fucosylation, while indolent cells display higher levels of fucosylation at sites N420 and N579. Additionally, treatment with either ICG-001 or E7386, which are both small molecule inhibitors of β-catenin/CBP signaling, leads to increased transcriptional expression of fucosyltransferases FUT2 and FUT3, with a concomitant increase in EGFR N-glycan antennary fucosylation. In order to discover which fucosylated glycan epitopes are involved in the observed effect, we performed in-depth characterization of multiply-fucosylated N-glycans via tandem mass spectrometry analysis of the EGFR tryptic glycopeptides. Data are available via ProteomeXchange with identifier PXD017060. We propose that β-catenin/CBP signaling promotes EGFR oncogenic activity in OSCC by inhibiting its N-glycan antennary fucosylation through transcriptional repression of FUT2 and FUT3.","journal":"Molecular Omics","year":2020,"id":79303,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9608,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":411952,"name":"Khalid Alamoud","orcid":"0000-0002-4929-8632","position":1,"is_corresponding":false},{"id":411953,"name":"Vanessa L. Stahl","orcid":"0000-0001-9953-3859","position":2,"is_corresponding":false},{"id":412869,"name":"Bach-Cuc Nguyen","orcid":null,"position":3,"is_corresponding":false},{"id":7644,"name":"Vinay K. Kartha","orcid":"0000-0002-2160-2196","position":4,"is_corresponding":false},{"id":411954,"name":"Manish V. Bais","orcid":"0000-0003-4198-7377","position":5,"is_corresponding":false},{"id":411955,"name":"K. Nomoto","orcid":"0000-0001-9553-0685","position":6,"is_corresponding":false},{"id":199965,"name":"Takashi Owa","orcid":null,"position":7,"is_corresponding":false},{"id":25431,"name":"Stefano Monti","orcid":"0000-0002-9376-0660","position":8,"is_corresponding":false},{"id":412870,"name":"Maria A. Kukuruzinska","orcid":null,"position":9,"is_corresponding":false},{"id":391253,"name":"Catherine E. Costello","orcid":"0000-0003-1594-5122","position":10,"is_corresponding":false},{"id":391250,"name":"Kevin Brown Chandler","orcid":"0000-0001-5514-9652","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T21:50:33.748601Z","pmid":"32203567","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}