Enolase 1 regulates stem cell-like properties in gastric cancer cells by stimulating glycolysis

Abstract

Recent studies have demonstrated that gastric cancer stem cells (CSCs) are a rare sub-group of gastric cancer (GC) cells and have an important role in promoting the tumor growth and progression of GC. In the present study, we demonstrated that the glycolytic enzyme Enolase 1 (ENO1) was involved in the regulation of the stem cell-like characteristics of GC cells, as compared to the parental cell lines PAMC-82 and SNU16, the expression of ENO1 in spheroids markedly increased. We then observed that ENO1 could enhance stem cell-like characteristics, including self-renewal capacity, cell invasion and migration, chemoresistance, and even the tumorigenicity of GC cells. ENO1 is known as an enzyme that is involved in glycolysis, but our results showed that ENO1 could markedly promote the glycolytic activity of cells. Furthermore, inhibiting glycolysis activity using 2-deoxy-d-glucose treatment significantly reduced the stemness of GC cells. Therefore, ENO1 could improve the stemness of CSCs by enhancing the cells’ glycolysis. Subsequently, to further confirm our results, we found that the inhibition of ENO1 using AP-III-a4 (ENOblock) could reduce the stemness of GC cells to a similar extent as the knockdown of ENO1 by shRNA. Finally, increased expression of ENO1 was related to poor prognosis in GC patients. Taken together, our results demonstrated that ENO1 is a significant biomarker associated with the stemness of GC cells.

Generation of the tumor-suppressive secretome from tumor cells

“…Eno1 (500 ng/mL, MBS2009113), and Ubc (500 ng/mL, MBS2029484, MyBioSource, San Diego, California, USA) recombinant proteins were given to EO771 cells, and cells were incubated for 24 h. A pharmacological inhibitor of Eno1 (ENOblock - AP-III-a4, MBS385406, MyBioSource) and an inhibitor of E3 ubiquitin ligase (Pomalidomide, MBS8005710, MyBioSource) were applied to the cells for 24 h 16 , 17 .…”

Extracellular Vesicle Transmission of Chemoresistance to Ovarian Cancer Cells Is Associated with Hypoxia-Induced Expression of Glycolytic Pathway Proteins, and Prediction of Epithelial Ovarian Cancer Disease Recurrence

“…In this study, we identified an increased expression of pyruvate kinase M1/2, enolase 1, and aldolase, fructose-bisphosphate A, in circulating extracellular vesicles of patients with ovarian cancer recurrence compared to the controls. Previously, these enzymes have been implicated in metabolic adaption, tumorigenesis, chemoresistance and patient survival [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. Multivariate models based on the expression of these proteins in extracellular vesicle delivered classification efficiencies of 73–100%.…”

The Indication of Poor Prognosis by High Expression of ENO1 in Squamous Cell Carcinoma of the Lung

“…Some scholars had different perspectives on the fact that patients with high ENO1 expression had a poor unwanted prognosis. Chinese patients with high expression of ENO1 had poor prognosis in a variety of cancers, including breast cancer [19], glioma [7], bladder cancer [9], pancreatic cancer [20], liver cancer [21], gastric cancer [33] (Chinese). However, Chang found that 46 patients with non-small cell lung cancer (NSCLC) whose expression of ENO1 was downregulated had a bad prognosis from American cohorts [17].…”

“…Overexpressed ENO1 had been observed in many tumor cells, and the upregulation of ENO1 expression might be correlated to aerobic glycolysis of cancer cells and the occurrence of malignant tumors [33]. Cancer cells largely depended on glycolysis to generate energy, and ENO1 was one of the vital enzymes that promoted cell glycolysis [5].…”