ArticleMolecular cell2018
Phosphorylation of EZH2 by AMPK Suppresses PRC2 Methyltransferase Activity and Oncogenic Function.
RetractedErratum issuedOpen access · bronzeAbstract read
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Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 111 papers, 1 of them a synthesis that pooled it.
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111citing papers in PubMed, 1 pooled it
8.3field-weighted citation impact, top 2% of its field
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Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 193 citations in OpenAlex.
- Phytochemicals regulate cancer metabolism through modulation of the AMPK/PGC-1α signaling pathway.BMC cancer · 2024Pooled it
- Machine learning-based multi-omic analysis identifies CEP55, DLGAP5, and EZH2 as regulated cell death biomarkers linked to immunotherapy resistance in hepatocellular carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- GFI1 enhances MHC-I expression in tumor cells and augments tumor responsiveness to PD-1/PD-L1 inhibitors.Cancer immunology, immunotherapy : CII · 2026Article
- Revisiting potential role of metformin in the circRNA-miRNA-mRNA axis: translational medicine perspectives in gastrointestinal cancer.Discover oncology · 2026Review
- AMPK-activated BAP1 regulates pVHL stability and tumor-suppressive functions.Cell death and differentiation · 2026Article
- Epigenetic landscape of the H3K27me3 mark in macrophages transformed by Theileria annulata.Communications biology · 2026Article
- Phosphorylation of CBX8 by PKD1 suppresses PRC1 activity and promotes cell senescence.Oncogene · 2026Article
- The plant epigenome governed by nutrients and metabolism.Current opinion in plant biology · 2025Review
- AMPK-Dependent Epigenetic Regulation of Metabolism Mediates the Anti-Cancer Action of Pterostilbene in Hepatocellular Carcinoma.Molecular nutrition & food research · 2025Article
- Computational exploration in search for novel natural product-derived EZH2 inhibitors for advancing anti-cancer therapy.Molecular diversity · 2025Article
- RAD51B-EZH2 axis as a potential therapeutic target for TNBC through cell fate conversion.Cell death & disease · 2025Article
- Targeting G9a-miScience · 2025Article
- Treating human cancer by targeting EZH2.Genes & diseases · 2025Review
- S-nitrosylation of EZH2 alters PRC2 assembly, methyltransferase activity, and EZH2 stability to maintain endothelial homeostasis.Nature communications · 2025Article
- Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance.Functional & integrative genomics · 2025Review
- Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential.Molecules (Basel, Switzerland) · 2024Review
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- Dietary phytosterols induce infertility in female mice via epigenomic modulations.Communications biology · 2024Article
- miR-4448/Girdin/Akt/AMPK axis inhibits EZH2-mediated EMT and tumorigenesis in small-cell lung cancer.Cancer medicine · 2024Article
- Endurance exercise-induced histone methylation modification involved in skeletal muscle fiber type transition and mitochondrial biogenesis.Scientific reports · 2024Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issued
Authors and funding
27 authors at 12 institutions in 4 countries.
Lixin WanDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: lixin.wan@moffitt.org.
Kexin XuDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Yongkun WeiDepartment of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jinfang ZhangDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Tao HanDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Christopher FryCell Signaling Technology, Danvers, MA 01923, USA.
Zhao ZhangDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Yao Vickie WangDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Liyu HuangDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Chinese National Human Genome Center at Shanghai, Shanghai 201203, PRC.
Min YuanDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Weiya XiaDepartment of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Wei-Chao ChangGraduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan.
Wen-Chien HuangDepartment of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
Chien-Liang LiuDepartment of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
Yuan-Ching ChangDepartment of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
Jinsong LiuDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yun WuDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Victor X JinDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Xiangpeng DaiDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Jianfeng GuoDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PRC.
Jia LiuDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, PRC.
Shulong JiangDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncology, Jining First People's Hospital, Jining, Shandong 272111, PRC; Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, PRC.
Jin LiDepartment of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Urology, 254th Hospital of PLA, Tianjin 300142, PRC.
John M AsaraDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Myles BrownDepartment of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: myles_brown@dfci.harvard.edu.
Mien-Chie HungDepartment of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan. Electronic address: mhung@mdanderson.org.
Wenyi WeiDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: wwei2@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · USThe University of Texas MD Anderson Cancer Center · USThe University of Texas Health Science Center at San Antonio · USMackay Memorial Hospital · TWHarvard University · USMoffitt Cancer Center · USCell Signaling Technology (United States) · USChina Medical University · TWChinese National Human Genome Center at Shanghai · CNDana-Farber Cancer Institute · USJining First People's Hospital · CNMolecular Oncology (United States) · US
Funding
Use of Organotypic and Mammary Gland Models to Investigate the Outcomes of ClonalP01CA080111 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI DILLON, DEBORAH · 1999 to 2018
$36.0MNovel regulation of PI3K/Akt to direct targeted breast cancer therapiesR01CA177910 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WEI, WENYI · 2013 to 2023
$3.9MInterplay between Cdh1 and major regulatory pathways in human cancerR01GM089763 · NIGMS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WEI, WENYI · 2009 to 2018
$3.0MOmics analysis of three-dimensional transcriptional regulationR01GM114142 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI JIN, VICTOR, LIN, SHILI · 2015 to 2024
$2.7MRational Combination Therapy with PARP Inhibitors in Triple Negative Breast CancerR01CA211615 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI YANG, LIUQING · 2017 to 2021
$2.1MFunctional analysis of beta-TRCP in cell cycle control and DNA damage responseR01GM094777 · NIGMS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WEI, WENYI · 2012 to 2015
$1.3MFunctional analysis of a tissue context-dependent role for beta-TRCP in lipid metabolism and tumorigenesisR01CA229307 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WEI, WENYI · 2018 to 2020
$1.1MA Novel Oncogenic Role for Cdc20 Implications in Adult T Cell Leukemia TreatmentR00CA183914 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI WAN, LIXIN · 2016 to 2018
$652kPolycomb -Independent Functions of EZH2 in Castration Resistant Prostate CancerR00CA178199 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI XU, KEXIN · 2015 to 2017
$498kA Novel Oncogenic Role for Cdc20 Implications in Adult T Cell Leukemia TreatmentK99CA183914 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WAN, LIXIN · 2014 to 2015
$339kElucidating a Novel Mechanism for SPOP in Suppressing Prostate TumorigenesisK99CA212292 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ZHANG, JINFANG · 2017 to 2018
$338kNCI NIH HHS K99 CA183914NCI NIH HHS K99 CA212292NCI NIH HHS P01 CA080111NCI NIH HHS R00 CA178199NCI NIH HHS R00 CA183914NCI NIH HHS R01 CA177910NCI NIH HHS R01 CA211615NCI NIH HHS R01 CA229307NIGMS NIH HHS R01 GM089763NIGMS NIH HHS R01 GM094777NIGMS NIH HHS R01 GM114142
Abstract
Sustained energy starvation leads to activation of AMP-activated protein kinase (AMPK), which coordinates energy status with numerous cellular processes including metabolism, protein synthesis, and autophagy. Here, we report that AMPK phosphorylates the histone methyltransferase EZH2 at T311 to disrupt the interaction between EZH2 and SUZ12, another core component of the polycomb repressive complex 2 (PRC2), leading to attenuated PRC2-dependent methylation of histone H3 at Lys27. As such, PRC2 target genes, many of which are known tumor suppressors, were upregulated upon T311-EZH2 phosphorylation, which suppressed tumor cell growth both in cell culture and mouse xenografts. Pathologically, immunohistochemical analyses uncovered a positive correlation between AMPK activity and pT311-EZH2, and higher pT311-EZH2 correlates with better survival in both ovarian and breast cancer patients. Our finding suggests that AMPK agonists might be promising sensitizers for EZH2-targeting cancer therapies.
Indexed as
AMP-Activated Protein KinasesAnimalsCarcinogenesisCell CycleCell Line, TumorCell ProliferationDNA-Binding ProteinsDNA MethylationEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticFemaleHistonesHumansMiceNeoplasm ProteinsNuclear ProteinsAMP-Activated Protein KinasesDNA-Binding ProteinsEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistonesNeoplasm ProteinsNuclear ProteinsPolycomb Repressive Complex 2SUZ12 protein, humanTranscription FactorsAMPKEZH2metforminovarian cancerphosphorylationpolycomb repressive complex 2
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