Evidence map›Paper›PMID 39915446›Full record

ArticleNature communications2025

ROS-induced cytosolic release of mitochondrial PGAM5 promotes colorectal cancer progression by interacting with MST3.

Shiyang Wang, Xi Wu, Wenxin Bi, Jiuzhi Xu, Liyuan Hou, Guilin Li, Yuwei Pan, Hanfu Zhang, Mengzhen Li, Sujuan Du and 12 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
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  5. bioRxiv : the preprint server for biology · 2026
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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

22 authors.

Shiyang Wang *State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
Xi Wu *State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
Wenxin BiState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
Jiuzhi XuKey Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, China Agricultural University, Beijing, China.
Liyuan HouKey Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, China Agricultural University, Beijing, China.
Guilin LiState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
Yuwei PanState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
Hanfu ZhangState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
Mengzhen LiState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
Sujuan DuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
Mingxin ZhangState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
Di LiuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
Shuiling JinDepartment of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Xiaojing ShiTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.ORCID http://orcid.org/0000-0002-5792-1287
Yuhua TianTianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Jianwei ShuaiWenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China.
Maksim V PlikusDepartment of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-8845-2559
Moshi SongState Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0000-0001-9929-8975
Zhaocai ZhouState Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-5441-3922
Lu YuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China. yulu@cau.edu.cn.ORCID http://orcid.org/0000-0002-6972-6489
Cong LvKey Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, China Agricultural University, Beijing, China. lvc@cau.edu.cn.
Zhengquan YuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China. zyu@cau.edu.cn.ORCID http://orcid.org/0000-0001-8696-2013

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82025006National Natural Science Foundation of China (National Science Foundation of China) 82230017National Natural Science Foundation of China (National Science Foundation of China) 82270588National Natural Science Foundation of China (National Science Foundation of China) 82341224
6 · The paper itself

Abstract

Aberrant release of mitochondrial reactive oxygen species (mtROS) in response to cellular stress is well known for promoting cancer progression. However, precise molecular mechanism by which mtROS contribute to epithelial cancer progression remains only partially understood. Here, using colorectal cancer (CRC) models, we show that upon sensing excessive mtROS, phosphatase PGAM5, which normally localizes to the mitochondria, undergoes aberrant cleavage by presenilin-associated rhomboid-like protein (PARL), becoming released into the cytoplasm. Cytosolic PGAM5 then directly binds to and dephosphorylates MST3 kinase. This, in turn, prevents STK25-mediated LATS1/2 phosphorylation, leading to YAP activation and CRC progression. Importantly, depletion of MST3 reciprocally promotes accumulation of cytosolic PGAM5 by inducing mitochondrial damage. Taken together, these findings demonstrate how mtROS promotes CRC progression by activating YAP via a post-transcriptional positive feedback loop between PGAM5 and MST3, both of which can serve as potential targets for developing next-generation anti-colon cancer therapeutics.

Indexed as

Colorectal NeoplasmsMitochondriaMitochondrial ProteinsPhosphoprotein PhosphatasesProtein Serine-Threonine KinasesReactive Oxygen SpeciesSerine-Threonine Kinase 3Adaptor Proteins, Signal TransducingAnimalsCell Line, TumorCytosolDisease ProgressionHCT116 CellsHippo KinasesHumansMiceAdaptor Proteins, Signal TransducingHippo KinasesLATS1 protein, humanLATS2 protein, humanMitochondrial ProteinsPGAM5 protein, humanPhosphoprotein PhosphatasesProtein Serine-Threonine KinasesReactive Oxygen SpeciesSerine-Threonine Kinase 3STK3 protein, humanTranscription FactorsTumor Suppressor ProteinsYAP1 protein, humanYAP-Signaling Proteins

Identifiers

PMID39915446
PMCPMC11802746

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.