Pyruvate carboxylase promotes SREBP1a-mediated lipid synthesis in epithelial ovarian cancerDownload PDF Download PDF ArticleOpen accessPublished: 14 May 2026Xinyun Huang1,2 na1,Huan Shi3 na1,Weiyan Shan3,Jingxia Zhang3,Qiaoping Xu ORCID: orcid.org/0000-0002-8327-735X2 &…Hongkai Shang ORCID: orcid.org/0009-0004-6922-67181,2 Communications Biology (2026) Cite this article We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.SubjectsMolecular biologyOncologyAbstractEpithelial ovarian cancer (EOC) is characterized by late diagnosis and high recurrence, with dysregulated lipid metabolism emerging as a hallmark of progression. Here, we identify pyruvate carboxylase (PC) as a key metabolic driver that promotes lipid synthesis in EOC. PC is upregulated in EOC tissues and correlates with poor prognosis and triglyceride accumulation. Mechanistically, PC enhances acetyl-CoA production, promoting sterol regulatory element-binding protein 1a (SREBP1a) acetylation and stability, and increases α-ketoglutarate levels to facilitate ten-eleven translocation 1 (TET1)-mediated DNA hydroxymethylation at lipid synthetase gene promoters. These dual effects augment SREBP1a recruitment and transcriptional activation of lipid synthesis genes. Pharmacological or genetic inhibition of PC, TET1, and SREBP1a, either individually or in combination, effectively suppresses lipid synthesis and tumor growth in vitro and Balb/c nude mouse xenografts. Our findings uncover a PC–TET1–SREBP1a metabolic-epigenetic axis for EOC lipid reprogramming and tumor progression, offering a potential therapeutic target to suppress ovarian cancer aggressiveness.The alternative text for this image may have been generated using AI.AcknowledgementsThe authors thank Bestcell Model Biological Center (Wuhan, China) for technical support. This work was supported by the National Natural Science Foundation of China (82171659), Zhejiang Provincial Natural Science Foundation of China (Y21H040001), Zhejiang Province Medical and Health Science and Technology (2023KY933), Zhejiang Traditional Chinese Medicine Science and Technology (2023ZL565), Zhejiang Traditional Chinese Medicine (2022ZA139), the Construction Fund of Key Medical Disciplines of Hangzhou (2025HZZD02) and the Construction Fund of Key Medical Disciplines of Hangzhou (2025HZZD07).Author informationAuthor notesThese authors contributed equally: Xinyun Huang, Huan Shi.Authors and AffiliationsZhejiang University School of Medicine, Hangzhou, ChinaXinyun Huang & Hongkai ShangAffiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, ChinaXinyun Huang, Qiaoping Xu & Hongkai ShangThe Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou First People’s Hospital, Hangzhou, ChinaHuan Shi, Weiyan Shan & Jingxia ZhangAuthorsXinyun HuangView author publicationsSearch author on:PubMed Google ScholarHuan ShiView author publicationsSearch author on:PubMed Google ScholarWeiyan ShanView author publicationsSearch author on:PubMed Google ScholarJingxia ZhangView author publicationsSearch author on:PubMed Google ScholarQiaoping XuView author publicationsSearch author on:PubMed Google ScholarHongkai ShangView author publicationsSearch author on:PubMed Google ScholarCorresponding authorsCorrespondence to Qiaoping Xu or Hongkai Shang.Ethics declarationsCompeting interestsThe authors declare no competing interests.Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationSupplementary Information (download PDF )Description of Additional Supplementary Files (download PDF )Supplementary Data (download XLSX )Reporting Summary (download PDF )Rights and permissionsOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints and permissionsAbout this articleDownload PDF