ATRA has been reported for its function in treating acute promyelocytic leukaemia patients.[25] An increasing number of studies have demonstrated that ATRA inhibits TIC properties in various solid cancer types.[26] For example, ATRA promotes the differentiation of GBM stem cells and thus suppresses tumor growth by regulating the Notch pathway.[26b] Here, we found that ATRA suppressed ESCC tumor initiation and progression by promoting OTUD6B translation and inhibiting TIC properties of ESCC cancer cells. This evidence concerns the gene OTUD6B and esophageal squamous cell carcinoma.