NF-кB determines the carcinogenic potential of necroptosis in liver

This sequence is driven by NF-кB-dependent transcription of inflammatory and mitogenic cytokines like IL-6, MCP-1 and CCL20, which are released directly from necroptotic hepatocytes, serving as damage-associated-molecular-patterns (DAMPs) / alarmins to promote inflammation, hepatocyte- and oval-cell-proliferation, genetic alterations and hepatocarcinogenesis. In line, we identified an NF-кB-necroptosis-signature in human HCCs associated with an unfavorable patients' prognosis.

In contrast, absence of NF-кB activation switches necroptosis towards a hypo-reactive, anti-carcinogenic form of cell-death. These results reveal that parenchymal NF-кB activation serves as an intracellular relay determining the reactivity and carcinogenic potential of PCD pathways.