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PLoS One ; 11(12): e0167857, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27978536

RESUMO

BACKGROUND: Recent studies indicated that some glycolytic enzymes are complicated, multifaceted proteins rather than simple components of the glycolytic pathway. FBP1 plays a vital role in glucose metabolism, but its role in gastric cancer tumorigenesis and metastasis has not been fully understood. METHODS: The prognostic value of FBP1 was first studied in The Cancer Genome Atlas (TCGA) database and validated in in-house database. The effect of FBP1 on cell proliferation and metastasis was examined in vitro. Nonparametric test and Log-rank test were used to evaluate the clinical significance of FBP1 expression. RESULTS: In the TCGA cohort, FBP1 mRNA level were shown to be predictive of overall survival in gastric cancer (P = 0.029). In the validation cohort, FBP1 expression were inversely correlated with advanced N stage (P = 0.021) and lymphovascular invasion (P = 0.011). Multivariate Cox regression analysis demonstrated that FBP1 was an independent predictor for both overall survival (P = 0.004) and disease free survival (P<0.001). Functional studies demonstrated that ectopic FBP1 expression inhibited proliferation and invasion in gastric cancer cells, while silencing FBP1 expression had opposite effects (P<0.05). Mechanically, FBP1 serves as a tumor suppressor by inhibiting epithelial-mesenchymal transition (EMT). CONCLUSIONS: Downregulation of FBP1 promotes gastric cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in gastric cancer.


Assuntos
DNA Helicases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Invasividade Neoplásica/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Prognóstico , Proteínas de Ligação a RNA , Neoplasias Gástricas/genética
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