Abstract
BackgroundGastric cancer (GC) is one of the most common gastrointestinal malignancies worldwide. Emerging evidence indicates that hyperglycemia promotes tumor progression, especially the processes of migration, invasion and epithelial–mesenchymal transition (EMT). However, the underlying mechanisms of GC remain unclear.MethodData from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to detect the expression of glycolysis-related enzymes and EMT-related transcription factors. Small interfering RNA (siRNA) transfection was performed to decrease ENO1 expression. Immunohistochemistry (IHC), Western blot and qRT-PCR analyses were used to measure gene expression at the protein or mRNA level. CCK-8, wound-healing and Transwell assays were used to assess cell proliferation, migration and invasion.ResultsAmong the glycolysis-related genes, ENO1 was the most significantly upregulated in GC, and its overexpression was correlated with poor prognosis. Hyperglycemia enhanced GC cell proliferation, migration and invasion. ENO1 expression was also upregulated with increasing glucose concentrations. Moreover, decreased ENO1 expression partially reversed the effect of high glucose on the GC malignant phenotype. Snail-induced EMT was promoted by hyperglycemia, and suppressed by ENO1 silencing. Moreover, ENO1 knockdown inhibited the activation of transforming growth factor β (TGF-β) signaling pathway in GC.ConclusionsOur results indicated that hyperglycemia induced ENO1 expression to trigger Snail-induced EMT via the TGF-β/Smad signaling pathway in GC.
Highlights
Gastric cancer (GC) is one of the most common gastrointestinal malignancies worldwide
Among the glycolysis-related genes, enolase 1 (ENO1) was the most significantly upregulated in GC, and its overexpression was correlated with poor prognosis
Decreased ENO1 expression partially reversed the effect of high glucose on the GC malignant phenotype
Summary
Gastric cancer (GC) is one of the most common gastrointestinal malignancies worldwide. Emerging evidence indicates that hyperglycemia promotes tumor progression, especially the processes of migration, invasion and epithelial–mesenchymal transition (EMT). Gastric cancer (GC) is the fifth most common malignancy worldwide, and the third leading cause of cancerrelated mortality [1]. It is widely known that metabolic syndrome plays an important role in GC and influences the prognosis of cancer patients [2]. Many GC patients are at an advanced stage when diagnosed and have a poor prognosis, and metastasis is the major reason for cancer-related death [7]. Previous studies have revealed that hyperglycemia contributes to cell invasion and metastasis in multiple cancers [8, 9]. Recent investigations have shown that epithelial– mesenchymal transition (EMT) is a reversible cellular
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