Evidence map›Paper›PMID 41530530›Full record

ArticleNature chemical biology2026

GCN5-ERK lactylation-phosphorylation loop amplifies lactate-driven cancer progression.

Bingsong Huang, Mingpeng Jin, Gaofeng Cui, Zhe Wang, Feng Wang, Mu Chen, Lei Zhu, Yunxuan Li, Xiaoning Yang, Rui Li and 17 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

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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

27 authors.

Bingsong Huang *Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID http://orcid.org/0000-0002-6481-1764
Mingpeng Jin *Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Gaofeng Cui *Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-5267-9033
Zhe Wang *State Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Feng WangState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Mu ChenDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Lei ZhuDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Yunxuan LiState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xiaoning YangCancer Research Center, Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai, China.
Rui LiState Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Jinhuan WuState Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Linhui ZhaiShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Yiming HeCancer Research Center, Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai, China.
Jie YangDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Xin DingState Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Qianwen WangState Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhen XvDepartment of Clinical Laboratory, The Affiliated East Hospital of Tongji University, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Yaobing OuyangDivision of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN, USA.
Jiale LiShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Yangbohui YangShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Ke LiState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID http://orcid.org/0000-0001-5634-6308
Zhenkun LouDivision of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-1938-3091
Georges MerDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-1900-1578
Jing ZhangDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China. zhangjingwt@tongji.edu.cn.ORCID http://orcid.org/0000-0003-3155-6768
Yuping ChenShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. 1610600@tongji.edu.cn.ORCID http://orcid.org/0000-0001-8562-0804
Jian YuanState Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China. yuanjian229@hotmail.com.ORCID http://orcid.org/0000-0002-2801-8849
Chunlong ZhongDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China. drchunlongzhong@tongji.edu.cn.ORCID http://orcid.org/0000-0002-0605-7273

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82225035, 32421002, 32090032, 82461160317, 32470767, 82172994, 82303058, and 82172820
6 · The paper itself

Abstract

The Warburg effect leads to increased lactate production and promotes cancer progression but the underlying mechanisms remain unclear. Here, we found that lactate activates the MAPK pathway through ERK lactylation, which promotes cancer progression. We identified GCN5 as the lactyltransferase responsible for ERK lactylation. Activated ERK phosphorylates GCN5, increasing its lactyltransferase activity toward ERK and establishing a positive feedback loop that amplifies lactate-mediated cancer progression. We provide evidence that lactylation of ERK at residue K231 weakens its interaction with MEK, thereby promoting ERK dimerization and activation. We developed a cell-penetrating peptide that specifically inhibits ERK lactylation. This peptide impairs tumor growth in KRAS-mutant cancer models. Taken together, our findings reveal a molecular mechanism by which lactate accelerates cancer progression through the ERK-GCN5 lactylation-phosphorylation cascade and suggest a strategy to disrupt ERK lactylation in RAS-ERK-driven cancers.

Indexed as

Extracellular Signal-Regulated MAP KinasesLactic AcidNeoplasmsAnimalsCell Line, TumorDisease ProgressionHumansMAP Kinase Signaling SystemMicePhosphorylationExtracellular Signal-Regulated MAP KinasesLactic Acid

Identifiers

PMID41530530

What OpenQuestion holds

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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 OpenQuestion graph.