Evidence map›Paper›PMID 40940446›Full record

ArticleEMBO reports2025

CDK1-mediated phosphorylation of LDHA fuels mitosis through LDHB-dependent lactate oxidation.

Mengting Liu, Aoxing Cheng, Weiyi You, Jiaxin Wu, Chenxu Dai, Ting Wang, Ying Wu, Fumei Zhong, Jue Shi, Yingying Du and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EMBO reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

18 authors.

Mengting Liu *Department of Digestive disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.ORCID 0009-0001-1052-8269
Aoxing Cheng *Department of Digestive disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.ORCID 0000-0001-9143-2199
Weiyi YouState Key Laboratory of Immune Response and Immunotherapy, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Jiaxin WuDepartment of Chemical Physics & Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China.ORCID 0009-0001-4715-9241
Chenxu DaiState Key Laboratory of Immune Response and Immunotherapy, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Ting WangState Key Laboratory of Immune Response and Immunotherapy, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Ying WuState Key Laboratory of Immune Response and Immunotherapy, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Fumei ZhongDepartment of Chemical Physics & Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China.
Jue ShiCenter for Quantitative Systems Biology, Department of Physics, Hong Kong Baptist University, Hong Kong, SAR, China.ORCID 0000-0003-4061-3496
Yingying DuDepartment of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Zhonghuai HouDepartment of Chemical Physics & Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China.
Ping GaoMedical Research Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.ORCID 0000-0002-6930-7989
Ke RuanDepartment of Chemical Physics & Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China.ORCID 0000-0001-9358-0451
Yi YangOptogenetics & Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai, 200237, China.
Yuzheng ZhaoOptogenetics & Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai, 200237, China. yuzhengzhao@ecust.edu.cn.ORCID 0000-0001-5400-0135
Kaiguang ZhangDepartment of Digestive disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China. zhangkaiguang@ustc.edu.cn.ORCID 0000-0001-9462-6335
Zhenye YangDepartment of Digestive disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China. zhenye@ustc.edu.cn.ORCID 0000-0001-7797-5891
Jing GuoDepartment of Digestive disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China. jguo2013@ustc.edu.cn.ORCID 0000-0002-0470-5417

Funding

Center for Advanced Interdisciplinary Science and Biomedicine of IHM of USTC QYPY20220017MOST | National Natural Science Foundation of China (NSFC) 31970670MOST | National Natural Science Foundation of China (NSFC) 32170736MOST | National Natural Science Foundation of China (NSFC) 92357301National Key R&D Program of China 2022YFA1303100the Fundamental Research Funds for the Central Universities YD9100002028The strategic priority Research Program of the Chinese academy of sciences XDB0940101
6 · The paper itself

Abstract

While cancer cells overexpress lactate dehydrogenase A (LDHA) to support glycolytic flux and lactate production, the role of LDHB-which preferentially catalyzes lactate oxidation-remains unclear. Here, we demonstrate that LDHB, but not LDHA, is essential for mitotic progression in cancers. During mitosis, CDK1 phosphorylates LDHA at threonine 18, reducing its incorporation into the lactate dehydrogenase (LDH) tetramer. This results in LDHB-enriched tetramers that shift catalytic activity toward lactate oxidation, converting lactate and NAD⁺ into pyruvate and NADH. The generated NADH fuels oxidative phosphorylation and ATP production, thereby sustaining mitosis. Notably, LDHA-T18 phosphorylation occurs exclusively in tumor tissues. Our findings reveal a tumor-specific mechanism in which CDK1 reprograms LDH isoenzyme composition to direct lactate toward NADH production, ensuring energy homeostasis during mitosis. This underscores the therapeutic necessity of targeting both LDHA and LDHB in cancer.

Indexed as

CDC2 Protein KinaseLactic AcidL-Lactate DehydrogenaseMitosisAdenosine TriphosphateCell Line, TumorHeLa CellsHumansIsoenzymesLactate Dehydrogenase 5NADNeoplasmsOxidation-ReductionPhosphorylationAdenosine TriphosphateCDC2 Protein KinaseCDK1 protein, humanIsoenzymesLactate Dehydrogenase 5Lactic AcidLDHA protein, humanL-Lactate DehydrogenaseNADATPLactateLactate DehydrogenaseMitosisNADH

Identifiers

PMID40940446
PMCPMC12550033

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.