{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Brunton H"],"funding":["Italian Ministry of Health","Scottish Genome Partnership","Cancer Research UK","Australian Pancreatic Cancer Genome Initiative","MRC/EPSRC Glasgow Molecular Pathology Node","Associazione Italiana Ricerca Cancro","Garvin Institute of Medical Research","Core Services at the Cancer Research UK Beatson Institute","FP7 European Community Grant Cam-Pac","Susan Wojcicki and Dennis Tropper NIH","Cancer Australia","CRUK Glasgow Centre","ICGC Ontario Institute for Cancer Research","NHMRC","Landon Foundation","NIH","National Health and Medical Research Council of Australia","Italian Cancer Genome Project–Ministry of University","Pancreatic Cancer UK Future Research Leaders Fund","Medical Research Council","NCI NIH HHS","Pancreatic Cancer Research Fund","The Howat Foundation","Wellcome Trust","American Association for Cancer Research"],"pagination":["107625"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9511995"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(6)"],"pubmed_abstract":["Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic phenotypes. Loss of genes that drive endodermal lineage specification, HNF4A and GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3β) a key regulator of glycolysis. Pharmacological inhibition of GSK3β results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility t"],"journal":["Cell reports"],"pubmed_title":["HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer."],"pmcid":["PMC9511995"],"funding_grant_id":["C596/A18076","23526","R01 CA247516","24439","C29717/A17263","14276","1162556","1175759/2158447","103721/Z/14/Z","A29996","427601","A25233","P50 CA062924","A14276","602783","CA62924","535903","5R01CA150190-07","R01 CA150190","C29717/A18484","12182","1162860","25237","C596/A20921","P20 CA102701","25813","A25142","U01 CA224145","631701","21139","A17196","A23526","29996","P50 CA102701","1143699","FLF2015_04_Glasgow","25233","FIMP-CUP_J33G13000210001","RBAP10AHJB"],"pubmed_authors":["Kench JG","Williams N","Crawford M","Johns AL","Nagaraj S","Scardoni M","Allison S","Humphris JL","Christophi C","Patch AM","DiPietro R","Bailey PJ","Nikfarjam M","Crawford HC","Taylor D","James V","Cunningham R","Nourbakhsh E","Pavlakis N","Manning S","Froeling FEM","Xu C","Eshleman JR","Gill AJ","Cooper CL","Brunton H","McLeod D","Mawson A","Worthley C","Bajrami I","Duthie F","Leonard C","Christ A","Kelly S","Barbour AP","Newell F","Caligiuri G","Nones K","McKay CJ","Grimwood P","Gallagher J","Gulati A","Cloonan N","Chai M","Cooke SL","Glasgow Precision Oncology Laboratory","Zeps N","Wong R","Chang DK","Wolfgang CL","Quinn M","Sandroussi C","Hatzifotis M","Pearson JV","Grimmond SE","Mukhopadhyay D","Grimmond SM","Forest C","Beghelli S","Barry ST","Asghari R","Moran-Jones K","Steinmann A","Chen J","Curry E","Kassahn KS","Jones M","Brough R","Musgrove EA","Scarlett CJ","Shanks E","Lee HC","DeBoer B","Chou A","Evers L","Pettitt SJ","Pettit J","Papangelis V","Jamieson NB","Harliwong I","Merrett ND","Epari KP","Morgan RA","Grutzmann R","McDade B","Idrisoglu S","Ruszkiewicz AR","Fawcett JW","Pilarsky C","O'Rourke TJ","Mukhedkar S","Lawlor RT","Anderson M","Scarpa A","Toon C","Yeung S","Waddell N","O'Connnor C","Wood S","Dreyer S","Krisnan K","Dziubinski ML","Wani S","Martin P","Rooman I","Cosman PH","Upstill-Goddard R","Clouston AD","McGregor GA","Brooke-Smith ME","Fletcher DR","Paulus-Hock V","Chantrill LA","Miller DK","Slater K","Pleass HC","Schulick RD","Rowe SJ","Thomson G","Quek K","Tang H","Lam VW","Richardson A","Kazakoff S","Maitra A","Hodgin M","Feeney K","Chiang A","McElroy D","Martyn-Smith M","Lord CJ","Cowley MJ","Thomas MT","Sansom OJ","Wood D","Bailey UM","Simpson SH","Hodgkinson P","Wu J","Ballal M","Tempero MA","Bassi C","Chin VT","Biankin AV","Corbo V","Tan CP","Spry NA","Nguyen NQ","Watson C","Mountain A","Nixon C","Debrencini T","Nourse C","Giry-Laterriere M","Simeone DM","Hruban RH","Mead RS","Pajic M","Texler M","Guminski A","Australian Pancreatic Cancer Genome Initiative","Ismail K","Sutherland RL","Wilson PJ","Wright DW","Hair J","Pinese M","Garner IM","Samra JS","Ramsay D","Ashworth A","Nagrial AM","Laycock A","Petersen GM","Song S","Morton JP","Marshall J","Tao J","Fink JL","Holmes O","Beilin M","Rebus S","Pinho AV","Gongora M","Graham JS","Brancato ML","Joseph D","Daly RJ","Bruxner T","Pavey D","Iacobuzio-Donahue CA","Das A","Westwood P","Brown R"],"additional_accession":[]},"is_claimable":false,"name":"HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer.","description":"Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic phenotypes. Loss of genes that drive endodermal lineage specification, HNF4A and GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3β) a key regulator of glycolysis. Pharmacological inhibition of GSK3β results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility t","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 May","modification":"2026-05-28T01:09:31.093Z","creation":"2025-04-19T22:49:06.063Z"},"accession":"S-EPMC9511995","cross_references":{"pubmed":["32402285"],"doi":["10.1016/j.celrep.2020.107625"]}}