Proposed pathways for promotion (A) and progression genes (B) influenced by TLR4. A. Promotion genes primarily signal through or are involved in EGFR signaling which may lead to cell growth and eventual tumor development. Thus, the EGFR pathway may drive the proliferative response in mice deficient in Tlr4 and concurrently inhibit communication between cells (Gja1), thus providing a growth advantage. References for gene interactions not described in text: Ran, ; Myc, ; Hmag1, ; Tnc, ; Mina, , Timp2 . Symbols: red, genes increased in BALBLps-dmice 1 day Protocol 1; blue, genes decreased in BALBLps-dmice 1 day Protocol; green, genes increased in BALB mice 1 day Protocol 1. B. During progression, the combination of inflammation observed in BALBLps-dmice in concert with up-regulation of these and other immune response genes, the many inflammation and immune response genes that were down regulated in BALB mice, and the additional contribution of cell growth genes (e.g. SPP1; , MCP-1; , supports a role of TLR4 in protection against lung tumor progression. Symbols: red, genes increased in BALBLps-dtumors; blue, genes decreased in BALB tumors; green, genes increased in BALB tumors; grey, protein changes in uninvolved tissue from the BALBLps-dmice. *Also decreased in BALB uninvolved tissue; **Also increased in BALBLps-duninvolved tissue. Abbreviations: Ccr2, chemokine (C-C motif) receptor 1; Chst1, carbohydrate sulfotransferase 1, Cxcl2, chemokine (C-X-C motif) ligand 2; Enpp2, ectonucleotide phosphodiesterase 2; Il1rn, interleukin 1 receptor antagonist; S100a8, S100 calcium binding protein A8; Timp2, tissue inhibitor of metalloproteinases; Utrn, utrophin.