Fig. 9
A plausible model of p-FoxM1S25-based monocyte recruitment, TAM polarization, angiogenesis, immune escape, and metastasis. In the cytoplasm, PLK1 phosphorylates FoxM1 at S25 in TGF-β-induced EMT, which triggers the nuclear translocation of p-FoxM1. p-FoxM1S25 directly activates STING, FOS, STAT1, IL1A, IL1B, IL6, VEGFA, CD274, and SNAI1 by direct binding to their promoters in the nucleus. Additionally, activated STAT1 and AP-1 (A complex of c-Fos/c-Jun) signaling facilitates the expression of IFITM1, CXCL1, IL1A, IL1B, IL6, VEGFA, CD274, and SNAI1. Upregulated IL1A, IL1B, CXCL1, and VEGFA trigger the recruitment of monocytes. IL6 induces TAM polarization. IFITM1 amplifies signaling through the upregulation of FoxM1. TGF-β and VEGFA secreted by TAM strengthen TGF-β-induced EMT of LUAD and angiogenesis in the TME, respectively. Expressed PD-L1 in LUAD escapes the immune checkpoint by binding with PD1 of TAM. Upregulated SNAI1 regulates the EMT and metastasis in LUAD