Evidence mapPaperPMID 42601451Full record

ArticleNature cell biology2026

An EZH2-SREBP2 axis promotes cholesterol biosynthesis and represents a noncanonical vulnerability in tumorigenesis.

Arum Kim, Bo Pan, Xufen Yu, Xing Gao, Nelli Khudaverdyan, Fatemeh Taherian, Chenxi Xu, Haiqing Zhong, Yan Xiong, H Ümit Kaniskan and 5 more

Abstract read
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In one paragraph

Article in Nature cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Arum KimDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0003-4207-4035
Bo PanDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0002-2626-1589
Xufen YuDepartments of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-7794-7890
Xing GaoDepartments of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nelli KhudaverdyanDepartment of Biochemistry, University of California, Riverside, CA, USA.
Fatemeh TaherianDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
Chenxi XuDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.
Haiqing ZhongDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0002-8152-1689
Yan XiongDepartments of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-3862-3663
H Ümit KaniskanDepartments of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-5327-832X
Masoud VedadiDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-0574-0169
Jikui SongDepartment of Biochemistry, University of California, Riverside, CA, USA.ORCID http://orcid.org/0000-0002-4958-1032
Jian JinDepartments of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-2387-3862
Ling CaiDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA. ling.cai@duke.edu.ORCID http://orcid.org/0000-0003-1240-3045
Gang Greg WangDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA. greg.wang@duke.edu.ORCID http://orcid.org/0000-0002-7210-9940

Funding

Targeting histone methyltransferase EZH2 for the treatment of hematological cancerF32CA261118 · DUKE UNIVERSITY · 2025 to 2025
$88k
U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) F32CA261118U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01-CA268384U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01-CA268519
6 · The paper itself

Abstract

Enhancer of zeste homolog 2 (EZH2) is frequently overexpressed in cancer, correlating with adverse clinical outcomes. However, how EZH2 overexpression supports tumorigenicity is not fully elucidated. Here we identify a previously unexplored tumour-promoting axis involving EZH2-SREBP2 association. EZH2 and SREBP2, a master regulator of lipid metabolism, cooperate to drive high expression of mevalonate pathway genes, enhancing cholesterol biosynthesis and sustaining tumour growth. Transcriptional activation domains of EZH2 and SREBP2 bind p300 directly, mediating proto-oncogene activation. Furthermore, we employed proteolysis targeting chimeras (PROTACs) to target this non-canonical EZH2 function. Independent EZH2-targeting PROTACs degrade both EZH2 and SREBP2, downregulating SREBP2-associated gene-expression programmes and inhibiting tumour growth. Collectively, this study unveils an EZH2-SREBP2 regulatory axis that promotes cholesterol biosynthesis and fuels tumorigenesis, shifting the current paradigm of EZH2's oncogenic functions.

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Registered trials

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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 Socratic graph.