Supplementary Figure 5: Model of EGFR signalling in hepatocytes and Kupffer cells during HCC formation.
From: EGFR has a tumour-promoting role in liver macrophages during hepatocellular carcinoma formation
EGFR signalling is hepatoprotective during DEN-induced liver damage as in the absence of EGFR, hepatocytes undergo more necrosis and apoptosis thus leading to increased IL-1β production and release. IL-1β stimulation of Kupffer cells in turn leads to release of IL-6, which is required for compensatory proliferation and repair of damaged hepatocytes. IL-1β-induced IL-6 production occurs in a bimodal way involving the activation of the IL-1R/MyD88 pathway to first induce EGFR ligands and ADAM17 expression with subsequent EGFR transactivation required for IL-6 production via JNK, p38 and IKK.
