{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["16(1)"],"submitter":["Chen F"],"pubmed_abstract":["Disrupted pH homeostasis can precipitate cell death and represents a viable therapeutic target in oncological interventions. Here, we utilize mass spectrometry-based drug analysis, transcriptomic screens, and lipid metabolomics to explore the metabolic mechanisms underlying pH-dependent cell death. We reveal CYP51A1, a gene involved in cholesterol synthesis, as a key suppressor of alkalization-induced cell death in pancreatic cancer cells. Inducing intracellular alkalization by the small molecule JTC801 leads to a decrease in endoplasmic reticulum cholesterol levels, subsequently activating SREBF2, a transcription factor responsible for controlling the expression of genes involved in cholesterol biosynthesis. Specifically, SREBF2-driven upregulation of CYP51A1 prevents cholesterol accumula"],"journal":["Nature communications"],"pagination":["2278"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11889236"],"repository":["biostudies-literature"],"pubmed_title":["CYP51A1 drives resistance to pH-dependent cell death in pancreatic cancer."],"pmcid":["PMC11889236"],"pubmed_authors":["Liu J","Li C","Kang R","Chen F","Tang D","Tang H"],"additional_accession":[]},"is_claimable":false,"name":"CYP51A1 drives resistance to pH-dependent cell death in pancreatic cancer.","description":"Disrupted pH homeostasis can precipitate cell death and represents a viable therapeutic target in oncological interventions. Here, we utilize mass spectrometry-based drug analysis, transcriptomic screens, and lipid metabolomics to explore the metabolic mechanisms underlying pH-dependent cell death. We reveal CYP51A1, a gene involved in cholesterol synthesis, as a key suppressor of alkalization-induced cell death in pancreatic cancer cells. Inducing intracellular alkalization by the small molecule JTC801 leads to a decrease in endoplasmic reticulum cholesterol levels, subsequently activating SREBF2, a transcription factor responsible for controlling the expression of genes involved in cholesterol biosynthesis. Specifically, SREBF2-driven upregulation of CYP51A1 prevents cholesterol accumula","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2025-04-04T01:43:01.1Z","creation":"2025-04-04T01:43:01.1Z"},"accession":"S-EPMC11889236","cross_references":{"pubmed":["40055353"],"doi":["10.1038/s41467-025-57583-2"]}}