Evidence map›Paper›PMID 42579622›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

EP300-Mediated MTF1-K218 Lactylation Buffers AR-Driven Copper Overload to Suppress Cuproptosis in Castration-Resistant Prostate Cancer.

Kai Li, Yong Wei, Yongshan Li, Yuxiang Dong, Jiancheng Lv, Mingzhi Yuan, Ao Shen, Fuyang Liu, Yetao Zhang, Youjian Li and 12 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 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

22 authors.

Kai LiDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.ORCID https://orcid.org/0009-0001-1658-750X
Yong WeiDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.ORCID https://orcid.org/0009-0002-9802-4061
Yongshan LiDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
Yuxiang DongDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
Jiancheng LvDepartment of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Mingzhi YuanJiangsu Key Laboratory of Intelligent Medical Image Computing, School of Artificial Intelligence, Nanjing University of Information Science and Technology, Nanjing, China.ORCID https://orcid.org/0000-0003-1322-7530
Ao ShenDigital Medical Research Center, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Fuyang LiuDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
Yetao ZhangDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
Youjian LiDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.ORCID https://orcid.org/0000-0003-4195-150X
Ruixi YuDepartment of Urology, Jiangnan University Medical Center, Wuxi, China.ORCID https://orcid.org/0009-0000-3949-232X
Yang LiuDepartment of Pathology, Wuxi People's Hospital, Wuxi, China.
Tong ZhaoDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
Jun WangDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
Kai ZhouDepartment of Urology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Zongyao FanDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
Manning WangDigital Medical Research Center, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Jun XuJiangsu Key Laboratory of Intelligent Medical Image Computing, School of Artificial Intelligence, Nanjing University of Information Science and Technology, Nanjing, China.ORCID https://orcid.org/0000-0001-5315-8811
Mulong DuDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.ORCID https://orcid.org/0000-0002-2733-6490
Min GuDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
Bing YaoNational Experimental Teaching Center of Basic Medical Science, Department of Medical Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.ORCID https://orcid.org/0000-0002-6657-2760
Qingyi ZhuDepartment of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.ORCID https://orcid.org/0009-0002-9570-2891

Funding

National Natural Science Foundation of China 82503824Scientific Research Project of Jiangsu Provincial Health Commission YJYC200506Scientific Research Project of Jiangsu Provincial Health Commission ZD2021028
6 · The paper itself

Abstract

Inducing cuproptosis for cancer therapy currently relies on supraphysiological copper or copper ionophores. Although serum copper is elevated in patients with prostate cancer, whether this is sufficient to trigger physiological cuproptosis remains unclear. Here, we show that tumor copper levels positively correlate with androgen receptor (AR) activity, and castration-resistant prostate cancer (CRPC) with hyperactivated AR exhibits pathological copper accumulation. AR activation enhances copper uptake while simultaneously conferring tolerance to copper toxicity, creating a buffered copper state. This adaptive response is mediated by metal-responsive transcription factor 1 (MTF1), which is transcriptionally upregulated by AR and undergoes EP300-dependent lactylation of lysine 218, promoting copper-induced nuclear translocation. Nuclear MTF1 activates metallothioneins (MT1E, MT1F, and MT1M) that sequester cytosolic copper and restrict mitochondrial copper accumulation. Disrupting MTF1 collapses this buffering system, enabling endogenous copper to trigger cuproptosis and suppress CRPC growth. These findings identify cuproptosis as a therapeutically exploitable vulnerability in CRPC.

Indexed as

androgen receptorcancer researchcoppercopper toxicitycytosoldownregulation and upregulationmetallothioneinmitochondrionprostate cancertranscription factor

Identifiers

PMID42579622
PMCPMC13460415

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.