Our laboratory first found that ribosomal S6 protein kinase 4 (RSK4) is highly expressed in ESCC CSCs, activates the β-catenin pathway through direct phosphorylation of GSK-3β at Ser9 and that RSK4 is a direct transcriptional target of ΔNp63α; thus, the ΔNp63α/RSK4/GSK-3β axis is key to driving CSC characterization and resistance to RT in ESCC [11]. This evidence concerns the gene RPS6KA6 and esophageal squamous cell carcinoma.