4.6 Article

Ezrin as a prognostic indicator regulates colon adenocarinoma progression through glycolysis

Journal

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
Volume 36, Issue 3, Pages 710-720

Publisher

WILEY
DOI: 10.1111/jgh.15195

Keywords

Colon adenocarcinoma; Ezrin; Glycolysis; Migration; Proliferation

Funding

  1. National Natural Science Foundation of China [31760313]
  2. Funds of Tumen River Scholar Project (2019)
  3. Key Laboratory of the Science and Technology Department of Jilin Province [20170622007JC]

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Our study revealed that Ezrin is upregulated in colon adenocarcinoma tissues and is associated with poor survival. Ezrin promotes proliferation, migration, and EMT in colon adenocarcinoma cells. It also significantly increases glucose uptake, lactate production, and ATP levels in these cells.
Background and Aim Aerobic glycolysis (the Warburg effect) is a distinctive metabolic hallmark of colon adenocarcinoma. Ezrin was a member of the Ezrin-Radixin-Moesin protein family and has been found profoundly implicated in tumorigenesis. However, the specific functional roles of Ezrin in metabolic reprogramming of colon adenocarcinoma remain poorly characterized and need to be explored. Methods The expression of Ezrin in colon adenocarcinoma tissues was screened by bioinformatics analysis and immunohistochemical assay. Si-RNA-mediated transfection and overexpression plasmid transfection were performed in colon adenocarcinoma cells. The proliferation viability was measured using MTT, colony formation, and EdU assays. The migration ability was determined using wound healing and transwell assay. The expression of EMT markers and transcriptional factors was detected using immunofluorescence staining and western blot assays. Glucose uptake, lactate production, and ATP assay were performed to validate the effect of Ezrin on glycolysis-mediated colon adenocarcinoma progression. Results Ezrin was upregulated in colon adenocarcinoma tissues and associated with poor survival. Ezrin stimulated colon adenocarcinoma cell proliferation, migration, and the process of EMT. Ezrin aroused significant increase in glucose uptake, lactate production, and ATP level in colon adenocarcinoma cells. Further investigations demonstrated that treatment with a glycolytic inhibitor 2-deoxy-d-glucose reversed the effects reduced by Ezrin on colon adenocarcinoma cells. Conclusions Our results evidenced a novel mechanism for colon adenocarcinoma cells proliferation and migration induced by Ezrin via glycolysis.

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