Evidence map›Paper›PMID 42373608›Full record

ArticleCell death & disease2026

Targeting EZH2-driven cholesterol metabolic vulnerability through Napabucasin suppresses ovarian cancer metastasis.

Mingjun Ma, Chao Wang, Yue Zhang, Shanshan Cheng, Jiani Yang, Yejun Zou, Xiu Tian, Sijia Gu, Jianxiao Li, Weiwei Cao and 16 more

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Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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26 authors.

Mingjun MaDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Chao WangDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Yue ZhangDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Shanshan ChengDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Jiani YangDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Yejun ZouDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Xiu TianDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Sijia GuDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Jianxiao LiDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Weiwei CaoDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Chao HuangDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Yaodi ShaoDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Yaqian ZhaoDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Yutong GaoDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Yilin LiuDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Wen PangDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Shuo ShiDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Hui DingDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Minghai ZhangDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Yifei CaiDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Yongsong WuDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Renhao XueDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID http://orcid.org/0000-0002-6608-9234
Xiawei ChengState Key Laboratory of Bioreactor Engineering, Optogenetics & Synthetic Biology Interdisciplinary Research Center, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, China.ORCID http://orcid.org/0000-0003-1833-9937
Chen ChuDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8084-0867
Jindan ShengDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China. shengjindan@tongji.edu.cn.ORCID http://orcid.org/0009-0000-7216-3958
Yu WangDepartment of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China. renjiwangyu@126.com.ORCID http://orcid.org/0000-0002-8683-6196

Funding

Health and Family Planning Committee of Pudong New Area (Health and Family Planning Committee of Pudong New District) PWZxq2022-03、PW2023D-14National Natural Science Foundation of China (National Science Foundation of China) 82072866, 82272888National Natural Science Foundation of China (National Science Foundation of China) 82303869Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 23YF1433400SJTU | School of Medicine, Shanghai Jiao Tong University (School of Medicine, Shanghai Jiao Tong University) YG2022ZD005
6 · The paper itself

Abstract

Ovarian cancer represents the most lethal gynecologic malignancy, with tumor metastasis being the primary contributor to patient mortality. EZH2, frequently overexpressed in various cancers, has been implicated in promoting metastatic progression through metabolic dysregulation. However, the mechanistic basis by which EZH2 reprograms cholesterol metabolism to facilitate ovarian cancer metastasis remains poorly defined. In this study, we demonstrated that EZH2 is highly expressed in both primary and metastatic ovarian cancer tissues, correlating positively with poor clinical prognosis. Genetic silencing of EZH2 significantly suppressed tumor proliferation and metastatic dissemination. Mechanistically, EZH2 overexpression activated the NF-κB-Rap1A signaling axis and orchestrated cholesterol metabolic reprogramming by activating SREBP2, while repressing TMED10, to promote ovarian cancer metastasis. Furthermore, we identified Napabucasin as a potent suppressor of EZH2/Rap1A axis and cholesterol metabolism. Notably, Napabucasin effectively inhibited ovarian cancer metastasis in vivo. Collectively, our findings elucidate a previously unrecognized mechanism by which EZH2 governs metastatic progression through cholesterol metabolic rewiring and propose Napabucasin as a promising therapeutic strategy for ovarian cancer, particularly in tumors with EZH2 hyperactivation.

Indexed as

CholesterolEnhancer of Zeste Homolog 2 ProteinOvarian NeoplasmsAnimalsCell Line, TumorCell MovementCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMiceMice, NudeNeoplasm MetastasisSignal TransductionCholesterolEnhancer of Zeste Homolog 2 ProteinEZH2 protein, human

Identifiers

PMID42373608
PMCPMC13315729

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.