fig7

Figure 7. Mechanism underlying the modulating effect of ZEB2 on cytokine secretion. (A) The binding motif of ZEB2 quoted from previous research[35]; (B) Schematic illustration showing that the binding motif of ZEB2 and its palindromic sequence could match several regions of the potential promoter sequences of CSF-1, IL4, and CCL8; (C) Relative luciferase activity in 293T cells transfected with plasmids containing CSF-1 or IL4 or CCL8 promoter (GV534-Promoter-OE), a plasmid expressing ZEB2 (GV712-ZEB2-OE), and the corresponding empty vector; (D) Schematic illustration indicating that, in a PI3K-Akt-dependent manner, ZEB2 is upregulated following EGFR-TKI resistance. This upregulation promotes M2 polarizaiton and inhibits M1 polarization of TAMs by increasing the secretion of CSF-1 and TGF-β1 in NSCLC. ***P < 0.0005.