However, a bulk of evidence also indicates STAT1 as a tumor promoter in the specific context.43–47 It has been reported that DNA DSBs can trigger the activation of STAT1 signaling25 and aberrant STAT1 activation may confer protection from IR in cancer cells.26,45,47 In the present study, we have observed that STAT1 is substantially upregulated in ESCC cells with high VAV2 but low γ-H2AX (Fig. 5), suggesting that STAT1 may be regulated by VAV2 or VAV2/Ku70/Ku80 complex but not directly associated with the events of DNA DSBs. This evidence concerns the gene XRCC5 and esophageal squamous cell carcinoma.