Abstract
The entry of metastatic cancer cells into the liver can trigger a rapid inflammatory response with increased local production of tumor necrosis factor α (TNFα). We investigated the molecular mechanisms that protect tumor cells from TNFα-induced apoptosis. A molecular crosstalk between the TNFα/TNFR/NFκB and IGF-IR/PI3-K/AKT pathways was identified that leads to autocrine IL-6/IL-6R/STAT3 signaling, rendering tumor cells resistant to cell death and enabling the metastatic colonization of the liver.