Evidence map›Paper›PMID 42728262›Full record

ArticleSignal transduction and targeted therapy2026

Malic enzyme 1 senses L-lactate to determine tumor heterogeneity.

Si-Yi Cao, Kewen Hu, Shijing Huang, Xiao-Lin Guan, Jian Wang, Yuan Shen, Hui Ming, Aihong Gu, Chao Wang, Xiao Shen and 5 more

Abstract read
In one paragraph

Article in Signal transduction and targeted therapy, 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.

Si-Yi Cao *Fudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China.
Kewen Hu *Fudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China.
Shijing Huang *Fudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China.
Xiao-Lin Guan *Fudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China.
Jian WangFudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China.
Yuan ShenFudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China.
Hui MingFudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China.
Aihong GuFudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China.
Chao WangFudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China.
Xiao ShenFudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China.
Qing WuFudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China.
Zhengjun ChenShanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
Miao YinFudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China. miaoyin@fudan.edu.cn.ORCID http://orcid.org/0000-0001-7026-7067
Wenyu WenFudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China. wywen@fudan.edu.cn.ORCID http://orcid.org/0000-0002-0798-4730
Qun-Ying LeiFudan University Shanghai Cancer Center & School of Basic Medical Sciences and Institutes of Biomedical Sciences; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College, Fudan University, Shanghai, China. qlei@fudan.edu.cn.ORCID http://orcid.org/0000-0002-8547-8518

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

L-lactate is generally elevated in tumors and acts as a signaling molecule that promotes tumor progression. Here, we reveal that malic enzyme 1 (ME1) functions as a previously unrecognized sensor of L-lactate through direct binding at arginine 155 (R155), thereby potentiating malignancy. Mechanistically, L-lactate binding promotes the nuclear translocation of ME1, a process involving reduced acetylation at lysine 362 (K362) and facilitated by nuclear import of karyopherin-α 4 (KPNA4). Nuclear accumulation of ME1 enhances metastatic potential, which is correlated with increased interaction with hepatoma-derived growth factor (HDGF) and acquisition of an epithelial‒mesenchymal transition (EMT)-related phenotype. Under nutrient-deficient conditions, L-lactate promotes the assembly of a ME1-lactate dehydrogenase B (LDHB) complex, which enhances oxidative phosphorylation (OXPHOS) and increases ATP production, suggesting a metabolic adaptive mechanism that supports tumor cell survival. Notably, the ME1

Indexed as

Lactic AcidMalate DehydrogenaseAnimalsCell Line, TumorEpithelial-Mesenchymal TransitionHumansMetabolic ReprogrammingMiceOxidative PhosphorylationLactic AcidMalate Dehydrogenasemalate dehydrogenase (decarboxylating)

Identifiers

PMID42728262
PMCPMC13569829

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.