Hepatic metastasis of gastric cancer is associated with enhanced expression of ethanolamine kinase 2 via the p53-Bcl-2 intrinsic apoptosis pathway.
Br J Cancer
; 124(8): 1449-1460, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33531692
ABSTRACT
BACKGROUND:
Gastric cancer (GC) with hepatic metastasis has a poor prognosis. Understanding the molecular mechanisms involved in hepatic metastasis may contribute to the development of sensitive diagnostic biomarkers and novel therapeutic strategies.METHODS:
We performed transcriptome analysis of surgically resected specimens from patients with advanced GC. One of the genes identified as specifically associated with hepatic metastasis was selected for detailed analysis. GC cell lines with knockout of the candidate gene were evaluated in vitro and in vivo. Expression of the candidate gene was analysed in GC tissues from 300 patients.RESULTS:
Ethanolamine kinase 2 (ETNK2) was differentially upregulated in GC patients with hepatic metastasis. ETNK2 expression was elevated in GC cell lines derived from haematogenous metastases. ETNK2 knockout significantly suppressed proliferation, invasion, and migration; increased apoptosis; reduced Bcl-2 protein expression; and increased phosphorylated p53 expression. In mouse xenograft models, ETNK2 knockout virtually abolished hepatic metastasis. Stratification of GC patients based on ETNK2 mRNA level revealed significant associations between high ETNK2 tumour expression and both hepatic recurrence and worse prognosis.CONCLUSIONS:
Upregulation of ETNK2 in GC enhances hepatic metastasis, possibly via dysregulation of p53-Bcl-2-associated apoptosis. ETNK2 expression may serve as a biomarker for predicting hepatic recurrence and a therapeutic target.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Regulação para Cima
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Proteína Supressora de Tumor p53
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Fosfotransferases (Aceptor do Grupo Álcool)
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Proteínas Proto-Oncogênicas c-bcl-2
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Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article