The Transcription Factor ELK1 Promotes Esophageal Squamous Cell Carcinoma Progression by Activating the CDK4/Wnt/β-catenin Pathway

Abstract

Objective: To explore the biological functions and the mechanisms of ETS transcription factor ELK1 (ELK1) in esophageal squamous cell carcinoma (ESCC) cells. Methods: ELK1 expression in ESCC samples/cells was analyzed by the UALCAN database. ELK1 mRNA expression in ESCC tissue samples and cells was detected utilizing quantitative real-time PCR. Cell counting kit-8 method, BrdU assay and Transwell assays were employed for examining ESCC cell proliferation, migration, and invasion. The PROMO database was adopted to predict the binding sites of ELK1 and the cyclin-dependent kinase 4 (CDK4) promoter region. The binding status of ELK1 and CDK4 was predicted and verified by dual-luciferase reporter gene assay and chromatin co-immunoprecipitation qPCR assay. The effect of ELK1 on CDK4 expression was examined via western blot. The possibly related signaling pathways to CDK4 were predicted by the gene set enrichment analysis in the LinkedOmics database. Results: In ESCC tissues and cells, ELK1 was up-regulated and was associated with short survival of patients. Upregulating ELK1 promoted malignant phenotypes of ESCC cells; ELK1 knockdown exerted the opposite effect. ELK1 bound to the CDK4 promoter region; ELK1 overexpression facilitated CDK4 expression, whereas ELK1 knockdown inhibited CDK4 expression. CDK4 is enriched in the Wnt signaling pathway, and ELK1 overexpression boosted β-catenin expression. Conclusion: ELK1 promotes of CDK4 transcription, and activates Wnt/β-catenin pathway, thereby facilitating the ESCC malignant progression.