These findings demonstrate for the first time that the CDK7-YAP-LDHD axis could shift between the metabolic phenotypes and stemness-associated functions in differentiated ESCC cells and ESCC CSCs and raise the possibility that targeting the CDK7-YAP-LDHD axis metabolic checkpoint might be efficient for treating ESCC patients. This evidence concerns the gene CDK7 and esophageal squamous cell carcinoma.