Abstract
Krüppel‐like transcription factor (KLF) family is involved in tumorigenesis in different types of cancer. However, the importance of KLF family in gastric cancer is unclear. Here, we examined KLF gene expression in five paired liver metastases and primary gastric cancer tissues by RT‐PCR, and immunohistochemistry was used to study KLF8 expression in 206 gastric cancer samples. The impact of KLF8 expression on glycolysis, an altered energy metabolism that characterizes cancer cells, was evaluated. KLF8 showed the highest up‐regulation in liver metastases compared with primary tumours among all KLF members. Higher KLF8 expression associated with larger tumour size (P < 0.001), advanced T stage (P = 0.003) and N stage (P < 0.001). High KLF8 expression implied shorter survival outcome in both TCGA and validation cohort (P < 0.05). Silencing KLF8 expression impaired the glycolysis rate of gastric cancer cells in vitro. Moreover, high KLF8 expression positively associated with SUVmax in patient samples. KLF8 activated the GLUT4 promoter activity in a dose‐dependent manner (P < 0.05). Importantly, KLF8 and GLUT4 showed consistent expression patterns in gastric cancer tissues. These findings suggest that KLF8 modulates glycolysis by targeting GLUT4 and could serve as a novel biomarker for survival and potential therapeutic target in gastric cancer.
Highlights
Gastric cancer is the fourth most common cancer in the world[1] and the second most common cancer in China.[2]
These results suggested that KLF8 could promote tumour growth and metastases, contributing to poor prognosis in gastric cancer
KLF8 is aberrantly expressed in several types of human tumours and its high expression is significantly correlated with oncogenic transformation and tumour progression
Summary
Gastric cancer is the fourth most common cancer in the world[1] and the second most common cancer in China.[2]. | 5088 differentiation and migration.[9,10,11,12] KLF8 is a relatively new member of the KLF family and is a sequence‐specific DNA‐binding protein that recognizes the CACCC‐box element.[13,14] Recent studies demonstrated that KLF8 induces epithelial‐to‐mesenchymal transition (EMT), stem cell characteristics and drug resistance in various cancers.[15,16,17,18,19,20] KLF8 acts as a dual transcriptional factor that can either repress or activate transcription of target genes including β‐ catenin,[18] CXCR419 and E‐cadherin genes.[20] KLF8 is overexpressed in gastric cancer, and ectopic KLF8 plays vital roles in various pathological processes. Our results show that KLF8 can promote glycolysis in gastric cancer by targeting GLUT4
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