Multiple Factors Determine the Oncolytic or Carcinogenic Effects of TLRs Activation in Cancer

Figure 2

Endosomal TLR signals. TLR4 is illustrated as an example. TLR4 uses both TRIF and MyD88 as its adaptors. TLR4 recognizes LPS and associates TIRAP/Mal-MyD88 at the plasma membrane. This triggers cell surface TLR signaling. TLR4 is then endocytosed and binds TRIF via TRAM. A cascade of activations then occurs. Activated TRIF combines with NF-κB activating kinase-associated protein 1 (NAP1). NAP1 then activates TBK1 and this in turn induces IKKε activation. The latter then activates IRF3 and induces type I IFN expression. TRIF can promote TRAF3 to activate TBK1 and IKKε to induce type I IFN production. TRIF also activates RIP1. RIP1 then combines TAB2 and TAB3 to activate TAK1 and NEMO. This in turn causes NF-κB to produce proinflammatory cytokines. RIP1 also binds Fas-associated cell death domain (FADD) protein to activate procaspase-8. Activated procaspase-8 induces apoptosis.