{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE80nnn/GSE80392/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by array"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80392"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"NF-кB determines the carcinogenic potential of necroptosis in liver","description":"Background: Genetic inhibition of NF-кB in hepatocytes favors Caspase-8/3-dependent apoptosis driving hepatocellular carcinoma (HCC) development in mice, but NF-кB is hyper-active in most human HCCs. RIPK1-RIPK3-MLKL-dependent necroptosis represents an alternative form of programmed cell death (PCD). We show here that IкB-Kinase-(IKK)-dependent activation of NF-кB in hepatocytes induces a hyper-reactive form of cell-death responses towards necroptosis and thereby promotes hepatocarcinogenesis. 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.","dates":{"publication":"2026/06/01"},"accession":"GSE80392","cross_references":{"GSM":["GSM2125846","GSM2125845","GSM2125844","GSM2125843","GSM2125842","GSM2125852","GSM2125841","GSM2125851","GSM2125840","GSM2125850","GSM2125839","GSM2125838","GSM2125849","GSM2125848","GSM2125837","GSM2125847"],"GPL":["11533"],"GSE":["80392"],"taxon":["Mus musculus"]}}