Evidence map›Paper›PMID 36991117›Full record

ArticleOncogene2023

PRMT5 methylating SMAD4 activates TGF-β signaling and promotes colorectal cancer metastasis.

Anyi Liu, Chengxin Yu, Cheng Qiu, Qi Wu, Changsheng Huang, Xun Li, Xiaowei She, Kairui Wan, Lang Liu, Mao Li and 13 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
11.8field-weighted citation impact, top 1% of its field
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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

  1. Pooled it
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  16. Enhancing CD8Biomolecules · 2025
    Article
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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

23 authors at 5 institutions in 1 country.

Anyi LiuGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Chengxin YuGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Cheng QiuGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Qi WuGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Changsheng HuangGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Xun LiDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Xiaowei SheGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Kairui WanGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Lang LiuGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Mao LiGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Zhihong WangGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Yaqi ChenGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Fuqing HuGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Da SongGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Kangdi LiGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Chongchong ZhaoProtein Chemistry and Proteomics Facility, Tsinghua University Technology Center for Protein Research, Beijing, 100084, PR China.
Haiteng DengProtein Chemistry and Proteomics Facility, Tsinghua University Technology Center for Protein Research, Beijing, 100084, PR China.ORCID 0000-0001-9496-1280
Xuling SunDepartment of General Surgery, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832000, PR China.
Feng XuGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Senyan LaiGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Xuelai LuoGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Junbo HuGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China. jbhu@tjh.tjmu.edu.cn.ORCID 0000-0002-3582-999X
Guihua WangGI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, PR China. ghwang@tjh.tjmu.edu.cn.ORCID 0000-0001-5423-9357
Tongji Hospital · CNTsinghua University · CNHuazhong University of Science and Technology · CNHuazhong University of Science and Technology Hospital · CNShihezi University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Perturbations in transforming growth factor-β (TGF-β) signaling can lead to a plethora of diseases, including cancer. Mutations and posttranslational modifications (PTMs) of the partner of SMAD complexes contribute to the dysregulation of TGF-β signaling. Here, we reported a PTM of SMAD4, R361 methylation, that was critical for SMAD complexes formation and TGF-β signaling activation. Through mass spectrometric, co-immunoprecipitation (Co-IP) and immunofluorescent (IF) assays, we found that oncogene protein arginine methyltransferase 5 (PRMT5) interacted with SMAD4 under TGF-β1 treatment. Mechanically, PRMT5 triggered SMAD4 methylation at R361 and induced SMAD complexes formation and nuclear import. Furthermore, we emphasized that PRMT5 interacting and methylating SMAD4 was required for TGF-β1-induced epithelial-mesenchymal transition (EMT) and colorectal cancer (CRC) metastasis, and SMAD4 R361 mutation diminished PRMT5 and TGF-β1-induced metastasis. In addition, highly expressed PRMT5 or high level of SMAD4 R361 methylation indicated worse outcomes in clinical specimens analysis. Collectively, our study highlights the critical interaction of PRMT5 and SMAD4 and the roles of SMAD4 R361 methylation for controlling TGF-β signaling during metastasis. We provided a new insight for SMAD4 activation. And this study indicated that blocking PRMT5-SMAD4 signaling might be an effective targeting strategy in SMAD4 wild-type CRC.

Indexed as

Colorectal NeoplasmsProtein-Arginine N-MethyltransferasesSmad4 ProteinTransforming Growth Factor betaCell Line, TumorHumansNeoplasm MetastasisSignal TransductionTransforming Growth Factor beta1PRMT5 protein, humanProtein-Arginine N-MethyltransferasesSmad4 ProteinSMAD4 protein, humanTransforming Growth Factor betaTransforming Growth Factor beta1

Identifiers

PMID36991117
OpenAlexW4361295272

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.