Role of POU1F1 promoting the properties of stemness of gastric carcinoma through ENO1‐mediated glycolysis reprogramming

Abstract

AbstractCancer stem cells (CSCs), a rare subset of tumor cells, have been recognized as promotive role on tumor initiation and propagation. Among, aerobic glycolysis, widely clarified in multiple tumor cells, is the key for maintaining cancer stemness. Regrettably, it is largely unknown about the connection of cellular metabolic reprogramming and stemness in gastric carcinoma (GC). Two GC parental cells lines PAMC‐82 and SNU‐16 and their spheroids were obtained to determine the expression status of POU1F1 using quantitative real‐time PCR (qRT‐PCR) and western blotting analysis, respectively. Gain or loss‐of‐function assay was employed to assess its biological effects. Sphere formation and transwell assays were performed to evaluate the stem cell‐like traits, including self‐renewal capacity, migration and invasion. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted for determining the binding relationship of POU1F1 on ENO1 promoter region. Herein, aberrantly upregulated POU1F1 was observed in spheroids, compared with the parental PAMC‐82 and SNU‐16 cells, which promoted stem cell‐like traits, as representing increasing sphere formation, enhanced cell migration and invasion. Additionally, POU1F1 expression was positively with glycolytic signaling, as displaying increasing glucose consumption, lactic acid production, and extracellular acid ratio (ECAR). Furthermore, POU1F1 was identified to be a transcriptional activator of ENO1, of which overexpression remarkably abolished POU1F1 knockdown‐mediated blocking effects. Taken together, we draw a conclusion that POU1F1 facilitated the stem cell‐like properties of GC cells through transcriptionally augmenting ENO1 to enhance glycolysis.