High-risk endometrial cancer proteomic profiling reveals that FBXW7 mutation alters L1CAM and TGM2 protein levels.
Cancer
; 127(16): 2905-2915, 2021 08 15.
Article
em En
| MEDLINE
| ID: mdl-33872388
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Endométrio
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Molécula L1 de Adesão de Célula Nervosa
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Proteína 7 com Repetições F-Box-WD
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Proteína 2 Glutamina gama-Glutamiltransferase
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article