These data suggested that p70S6K1‐mediated phosphorylation of HDAC2 (Ser394) following TRIB2‐induced Akt/mTOR activation is essential for the epigenetic suppression of p21 and that it might promote CSC characteristics and radioresistance in ESCC. The gene discussed is TRIB2; the disease is esophageal squamous cell carcinoma.