Evidence map›Paper›PMID 42151565›Full record

ArticleCell research2026

Compression-induced metabolic adaptation drives confined tumor cell migration and distant metastasis via malate-dependent microtubule reinforcement.

Min Liu, Bing Liu, Chen Chen, Yi-Ran Wang, Xiaoyan Li, Yajuan Zhang, Xinyang Liu, Dingpei Zhou, Hong Gao, Yijun Qi and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell research, 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

16 authors.

Min Liu *Key Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Bing Liu *Key Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Chen Chen *Department of Radiation Oncology, Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yi-Ran WangShanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Xiaoyan LiKey Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Yajuan ZhangDepartment of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.ORCID 0009-0009-5002-2535
Xinyang LiuEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Dingpei ZhouKey Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Hong GaoKey Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Yijun QiKey Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
Chen SuNational Facility for Protein Science in Shanghai, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China.
Dong GaoKey Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0003-1821-2741
Yun ZhaoKey Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0002-7807-6094
Yan-Jun LiuShanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China. yanjun_liu@fudan.edu.cn.
Quanlin LiEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China. li.quanlin@zs-hospital.sh.cn.ORCID 0000-0002-9108-8786
Weiwei YangKey Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. wyang@sibcb.ac.cn.ORCID 0000-0002-1661-9137

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstactMetastasis, responsible for > 90% of cancer-related mortality, represents the most lethal yet least mechanistically understood phase of cancer progression. A critical bottleneck is tumor cell migration through physically confined environments, including dense extracellular matrix, narrow capillaries and endothelial gaps. Although tumor cells reprogram their metabolism to facilitate cancer progression, it remains unclear how specific metabolic adaptations enable them to overcome the unique physical challenges posed by these confined spaces, thereby promoting distant metastasis. We conducted a CRISPR screen targeting 1685 metabolic enzymes and identified dihydrolipoamide dehydrogenase (DLD), a mitochondrial enzyme involved in energy metabolism, as essential for confined migration of tumor cells. Depletion or pharmacological inhibition of DLD suppressed CRC metastasis by impairing tumor cell migration through capillaries and endothelial gaps. Upon mechanical compression, heterogeneous nuclear ribonucleoprotein A0 (hnRNPA0) binds to the adenylate uridylate-rich element (ARE) in the 3'UTR of DLD, enhancing its mRNA stability and upregulating DLD expression in tumor cells during confined migration. Elevated DLD expression enhances tricarboxylic acid (TCA) cycle metabolism, increasing malate levels. Malate interacts with tubulin alpha-1B chain (TUBA1B) to promote microtubule assembly, facilitating confined migration and metastasis. Knock-in of an ARE-deleted DLD mutant (DLD ΔARE) or disruption of the malate-TUBA1B interaction significantly suppressed tumor metastasis. In CRC patients, DLD expression was upregulated in tumor cells within capillaries of primary tumors and correlated with metastatic recurrence. Our findings reveal that compressive forces drive metastatic dissemination by epigenetically reprogramming mitochondrial metabolism, which in turn fuels cytoskeletal remodeling.

Indexed as

Cell MovementColorectal NeoplasmsMalatesMicrotubulesAdaptation, PhysiologicalAnimalsCell Line, TumorCitric Acid CycleHumansMetabolic ReprogrammingMiceNeoplasm MetastasisTubulinmalic acidTubulin

Identifiers

PMID42151565
PMCPMC13287788

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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.