{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Qian X"],"funding":["Ministry of Science and Technology of the People's Republic of China (MOST)","Ministry of Science and Technology of the People's Republic of China","Zhejiang University (ZJU)","MOST | National Natural Science Foundation of China (NSFC)","MOST | NSFC | NSFC-Zhejiang Joint Fund | Natural Science Foundation of Zhejiang Province","MOST | NSFC | NSFC-Zhejiang Joint Fund | Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents","Shanghai Municipal Human Resources and Social Security Bureau","MOST | National Natural Science Foundation of China","Zhejiang University","MOST | NSFC | NSFC-Zhejiang Joint Fund | Natural Science Foundation of Zhejiang Province (ZJNSF)"],"pagination":["e2412473122"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11804496"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["122(5)"],"pubmed_abstract":["Tumor cells reshape iron and lipid metabolism for their rapid proliferation. However, how tumor cells coordinate the interplay between tumor cell-specific iron homeostasis and lipid metabolism reprogramming to counteract energy shortages remains unclear. Here, we demonstrated that glucose deprivation in hepatocellular carcinoma (HCC) cells induced AMPK-dependent Transferrin S685 phosphorylation, which exposed Transferrin nuclear localization signal (NLS) for binding to importin α7 and subsequent nuclear translocation. Nucleus-translocated Transferrin interacts with PPARα and enhance its protein stability to increase fatty acid oxidation (FAO) upon glucose deprivation. Mechanistically, PPARα-associated Transferrin upregulates iron-dependent PHD2-mediated PPARα P87 hydroxylation and subseque"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Transferrin promotes fatty acid oxidation and liver tumor growth through PHD2-mediated PPARα hydroxylation in an iron-dependent manner."],"pmcid":["PMC11804496"],"funding_grant_id":["82072630","92157113","2020YFA0803300","2022R01006","82103658","82272406","No.2022PJD040","LQ22H160023","2021YFA0805600","188020*194221901/029","82173114","LD21H160003","82372814","2019YFA0905800","82188102","LD22H160002","82030074"],"pubmed_authors":["Guo Z","Hu Z","Wu Q","Lu Z","Lin Y","Ying H","Liu T","Hou Y","Wen T","Meng Y","Zhan P","Wang S","Chen X","Shen Y","Wang Z","Wu X","Dong B","Zhou Q","Xu D","Sun X","Zhou Y","Bai X","Li M","Qian X","Zhang W","Xiao L","Duan S","Ouyang Y","Duan Y","Wang KL","Tian Q","Liu G"],"additional_accession":[]},"is_claimable":false,"name":"Transferrin promotes fatty acid oxidation and liver tumor growth through PHD2-mediated PPARα hydroxylation in an iron-dependent manner.","description":"Tumor cells reshape iron and lipid metabolism for their rapid proliferation. However, how tumor cells coordinate the interplay between tumor cell-specific iron homeostasis and lipid metabolism reprogramming to counteract energy shortages remains unclear. Here, we demonstrated that glucose deprivation in hepatocellular carcinoma (HCC) cells induced AMPK-dependent Transferrin S685 phosphorylation, which exposed Transferrin nuclear localization signal (NLS) for binding to importin α7 and subsequent nuclear translocation. Nucleus-translocated Transferrin interacts with PPARα and enhance its protein stability to increase fatty acid oxidation (FAO) upon glucose deprivation. Mechanistically, PPARα-associated Transferrin upregulates iron-dependent PHD2-mediated PPARα P87 hydroxylation and subseque","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-03-18T14:04:43.625Z","creation":"2025-08-23T03:07:25.402Z"},"accession":"S-EPMC11804496","cross_references":{"pubmed":["39888917"],"doi":["10.1073/pnas.2412473122"]}}