{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Murthy D"],"funding":["U.S. Department of Health & Human Services | NIH | National Cancer Institute","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["613-627"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11021164"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(4)"],"pubmed_abstract":["The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment. Comparative H3K27ac ChIP-seq and RNA-seq analyses revealed alterations in polyamine homeostasis through regulation of SAT1 gene expression and enrichment of the SP1-responsive signature. We identified acetate/ACSS2-mediated ace"],"journal":["Nature cell biology"],"pubmed_title":["Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2-SP1-SAT1 axis."],"pmcid":["PMC11021164"],"funding_grant_id":["P30 CA036727","U54CA274329","P20 GM113126","P50 CA127297","P30 GM103335","R01CA270234","P20 GM121316","R01 CA270234","R01CA256911","T32 CA009476","R01 CA256911","R01CA163649","R01 CA163649","R37 CA276924","R37CA276924","P20 GM103447","U54 CA274329","P30 CA225520","R50 CA211462"],"pubmed_authors":["Rai V","Rana S","Kumar V","Hu T","Chaudhary S","Wellen KE","Thakur R","Wang D","Yu F","Klinkebiel DL","Souchek J","Black AR","Pacheco C","Natarajan A","Jain A","Lazenby AJ","Mehla K","Patel R","Chaika NV","Hollingsworth MA","Dasgupta A","Kollala SS","King RJ","Shukla SK","He C","Grandgenett PM","Singh PK","Powers R","Jha K","Mulder SE","Edil BH","Murthy D","Hwang RF","Attri KS","Gebregiworgis T","Ulhannan S","Ly Q"],"additional_accession":[]},"is_claimable":false,"name":"Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2-SP1-SAT1 axis.","description":"The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment. Comparative H3K27ac ChIP-seq and RNA-seq analyses revealed alterations in polyamine homeostasis through regulation of SAT1 gene expression and enrichment of the SP1-responsive signature. We identified acetate/ACSS2-mediated ace","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-05-29T17:47:28.142Z","creation":"2026-04-08T05:45:23.258Z"},"accession":"S-EPMC11021164","cross_references":{"pubmed":["38429478"],"doi":["10.1038/s41556-024-01372-4"]}}