Ezrin as a prognostic indicator regulates colon adenocarinoma progression through glycolysis

Abstract

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.

Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment

“…PDPN expression is upregulated peculiarly in the growing edge of tumors and commonly co-localized with ERM proteins ( 100 , 106 ). Similar to PDPN, overexpression of ERM proteins has been detected in various types of cancers: ezrin overexpression in breast, hepatocellular, colon, ovarian, and pancreatic cancers ( 137 – 141 ); radixin overexpression in pancreatic cancer with lymph node metastasis ( 142 ); moesin overexpression in skin cancer, colorectal carcinoma, endometrial adenocarcinoma, and glioma ( 143 – 146 ). Moreover, upregulation of ERM proteins is associated with poor prognosis in cancer patients ( 140 , 147 – 150 ).…”

A novel fatty acid metabolism‐related gene signature predicts the prognosis, tumor immune properties, and immunotherapy response of colon adenocarcinoma patients

“…7,8 As previously stated, cancer cells are sensitive to the "Warburg effect", which is characterized by increased glycolysis or aerobic glycolysis. 9 Along with aberrant glucose metabolism, dysregulation of lipid metabolism has received increased emphasis in the past few decades as a hallmark of metabolic reprogramming in cancer, particularly COAD. 10 The disruption of lipid metabolism, specifically for fatty acid metabolism with altered expression and activity of lipid-metabolizing enzymes as a result of abnormal activation of oncogenic signaling pathways, has been widely recognized as a critical factor of metabolic reconfiguration within cancer cells and immune cells that may lead to the long-term development of COAD.…”

“…Reprogramming the energy metabolism of tumors may enhance their fast growth, metastasis, proliferation, and survival, and is a newly recognized characteristic of cancer 7,8 . As previously stated, cancer cells are sensitive to the “Warburg effect”, which is characterized by increased glycolysis or aerobic glycolysis 9 . Along with aberrant glucose metabolism, dysregulation of lipid metabolism has received increased emphasis in the past few decades as a hallmark of metabolic reprogramming in cancer, particularly COAD 10 .…”