{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ravichandran M"],"funding":["NCI","NIDDK NIH HHS","NCI NIH HHS","NIH Director’s New Innovator Award","NIGMS NIH HHS","NIH NCI"],"pagination":["2198-2219"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9444964"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(9)"],"pubmed_abstract":["The mechanisms underlying metabolic adaptation of pancreatic ductal adenocarcinoma (PDA) cells to pharmacologic inhibition of RAS-MAPK signaling are largely unknown. Using transcriptome and chromatin immunoprecipitation profiling of PDA cells treated with the MEK inhibitor (MEKi) trametinib, we identify transcriptional antagonism between c-MYC and the master transcription factors for lysosome gene expression, the MiT/TFE proteins. Under baseline conditions, c-MYC and MiT/TFE factors compete for binding to lysosome gene promoters to fine-tune gene expression. Treatment of PDA cells or patient organoids with MEKi leads to c-MYC downregulation and increased MiT/TFE-dependent lysosome biogenesis. Quantitative proteomics of immunopurified lysosomes uncovered reliance on ferritinophagy, the sele"],"journal":["Cancer discovery"],"pubmed_title":["Coordinated Transcriptional and Catabolic Programs Support Iron-Dependent Adaptation to RAS-MAPK Pathway Inhibition in Pancreatic Cancer."],"pmcid":["PMC9444964"],"funding_grant_id":["K08 CA21842002","R37 CA230042","R37CA230042","K08 CA218420","DP2CA216364","R01 DK124384","T32 GM136547","R01CA240603","R01 CA240603","R01CA260249","P50CA127003","P50 CA127003","R01 CA260249","DP2 CA216364"],"pubmed_authors":["Kuljanin M","Hennessey CJ","Staes AAL","Perera RM","Yang A","Cakir Z","Venida A","Desousa BR","Jain IH","Mancias JD","Cai C","Yang Y","Hu J","DeNicola GM","Ravichandran M","Foakes C","Rademaker G","Shen Y","Aguirre AJ","Ward NP"],"additional_accession":[]},"is_claimable":false,"name":"Coordinated Transcriptional and Catabolic Programs Support Iron-Dependent Adaptation to RAS-MAPK Pathway Inhibition in Pancreatic Cancer.","description":"The mechanisms underlying metabolic adaptation of pancreatic ductal adenocarcinoma (PDA) cells to pharmacologic inhibition of RAS-MAPK signaling are largely unknown. Using transcriptome and chromatin immunoprecipitation profiling of PDA cells treated with the MEK inhibitor (MEKi) trametinib, we identify transcriptional antagonism between c-MYC and the master transcription factors for lysosome gene expression, the MiT/TFE proteins. Under baseline conditions, c-MYC and MiT/TFE factors compete for binding to lysosome gene promoters to fine-tune gene expression. Treatment of PDA cells or patient organoids with MEKi leads to c-MYC downregulation and increased MiT/TFE-dependent lysosome biogenesis. Quantitative proteomics of immunopurified lysosomes uncovered reliance on ferritinophagy, the sele","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2026-05-29T00:04:10.756Z","creation":"2025-04-07T05:08:24.111Z"},"accession":"S-EPMC9444964","cross_references":{"pubmed":["35771494"],"doi":["10.1158/2159-8290.cd-22-0044","10.1158/2159-8290.CD-22-0044"]}}