By modulating IL-4 expression using siRNA, recombinant IL-4, or anti-IL-4 antibody, we found that IR-induced IL-4 signaling activates Akt/JNK via JAK, which in turn enhances β-catenin/Sox2/Oct4/Stat6 signaling and subsequent MMP-2/9 activation, ultimately leading to tumor progression and stemness maintenance of human cancer cells (Figure 3E–3H and Supplementary Figure S2). Here, SOX2 is linked to cancer.