{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gu L"],"funding":["NCATS NIH HHS","NIDDK NIH HHS","NIA NIH HHS","NIEHS NIH HHS","NCI NIH HHS","NIH HHS"],"pagination":["461-469"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12168545"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["637(8045)"],"pubmed_abstract":["Hepatocellular carcinoma (HCC) originates from differentiated hepatocytes undergoing compensatory proliferation in livers damaged by viruses or metabolic-dysfunction-associated steatohepatitis (MASH)<sup>1</sup>. While increasing HCC risk<sup>2</sup>, MASH triggers p53-dependent hepatocyte senescence<sup>3</sup>, which we found to parallel hypernutrition-induced DNA breaks. How this tumour-suppressive response is bypassed to license oncogenic mutagenesis and enable HCC evolution was previously unclear. Here we identified the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) as a p53 target that is elevated in senescent-like MASH hepatocytes but suppressed through promoter hypermethylation and proteasomal degradation in most human HCCs. FBP1 first declines in metabolically stressed "],"journal":["Nature"],"pubmed_title":["FBP1 controls liver cancer evolution from senescent MASH hepatocytes."],"pmcid":["PMC12168545"],"funding_grant_id":["S10 OD032398","R01 DK120714","R01 DK137061","P01 AG073084","P01 CA281819","R01 ES030993","KL2 TR001444","R01 CA234128","R01 ES032547","R35 CA220483","R01 CA281784","R01 DK133930","R01 DK099205","R01 DK133448","R01 CA269919","P30 CA023100","P30 DK120515"],"pubmed_authors":["Nandi SP","Ganguly S","Zhu Y","Lee M","Carter KW","Dhar D","Liver Cancer Collaborative","Liu Y","Winteringham LN","Wallace MC","Gu L","Tibballs J","Simon MC","Carlessi R","Sauceda C","Alexandrov LB","Leedman PJ","Teneche MG","Adams PD","Dwyer BJ","Ohira M","Hosseini M","Sakane S","Kisseleva T","Watari K","Bareng B","Gonzalez DJ","Tirnitz-Parker JEE","Forrest ARR","Karin M"],"additional_accession":[]},"is_claimable":false,"name":"FBP1 controls liver cancer evolution from senescent MASH hepatocytes.","description":"Hepatocellular carcinoma (HCC) originates from differentiated hepatocytes undergoing compensatory proliferation in livers damaged by viruses or metabolic-dysfunction-associated steatohepatitis (MASH)<sup>1</sup>. While increasing HCC risk<sup>2</sup>, MASH triggers p53-dependent hepatocyte senescence<sup>3</sup>, which we found to parallel hypernutrition-induced DNA breaks. How this tumour-suppressive response is bypassed to license oncogenic mutagenesis and enable HCC evolution was previously unclear. Here we identified the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) as a p53 target that is elevated in senescent-like MASH hepatocytes but suppressed through promoter hypermethylation and proteasomal degradation in most human HCCs. FBP1 first declines in metabolically stressed ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-06-02T08:42:04.228Z","creation":"2026-04-16T03:12:30.149Z"},"accession":"S-EPMC12168545","cross_references":{"pubmed":["39743585"],"doi":["10.1038/s41586-024-08317-9"]}}