{"doi":"10.1002/cncr.33567","title":"High‐risk endometrial cancer proteomic profiling reveals that <i>FBXW7</i> mutation alters L1CAM and TGM2 protein levels","abstract":"BACKGROUND: FBXW7 is frequently somatically mutated in grade 3 endometrioid endometrial cancers (G3EECs) and serous endometrial cancers (SECs), which are high-risk cancers associated with poor outcomes and in need of novel treatment options. The aim of this study was to determine the proteomic effects of 3 FBXW7 mutations in high-risk endometrial cancers (ECs). METHODS: Clustered regularly interspaced short palindromic repeats (CRISPR) editing was used to generate 3 HEC-50B G3EEC derivative cell lines, each of which harbored 1 FBXW7 mutation, and to revert an endogenous FBXW7 mutation in HEC-1-B grade 2 endometrioid endometrial cancer (G2EEC) cells to the wild-type genotype. Proteomic profiling based on liquid chromatography-tandem mass spectrometry was used to determine protein differences between the HEC-50B derivative lines and parental cells. Western blot analysis was performed to assess differential protein levels of CRISPR-edited derivative lines originating from HEC-50B, ARK1 (SEC), ARK4 (SEC), HEC-1-B, and JHUEM-1 (G2EEC) cell lines in comparison with parental cells. RESULTS: Results of this study demonstrated the effects of FBXW7 mutations on the proteome and phosphoproteome of HEC-50B G3EEC cells and highlighted proteins that also exhibited altered levels in FBXW7-mutated ARK1 and ARK4 SEC cells, including 2 potentially druggable proteins: L1 cell adhesion molecule (L1CAM) and transglutaminase 2 (TGM2). Furthermore, they demonstrated that reversion of an endogenous FBXW7 mutation to the wild-type genotype in JHUEM-1 and HEC-1-B G2EEC cells resulted in decreased L1CAM and TGM2 protein levels. CONCLUSIONS: L1CAM and TGM2 protein levels are affected by FBXW7 mutations in ECs.","journal":"Cancer","year":2021,"id":181954,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8452,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":733658,"name":"Eun‐Jeong Yu","orcid":"0000-0002-2118-2128","position":1,"is_corresponding":false},{"id":442170,"name":"Daphne W. Bell","orcid":"0000-0001-7314-3932","position":2,"is_corresponding":false},{"id":442169,"name":"Mary Ellen Urick","orcid":"0000-0002-1032-504X","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:48:09.223560Z","pmid":"33872388","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":[]}