Evidence map›Paper›PMID 29235476›Full record

ArticleNature communications2017

Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7.

Zhengkui Zhang, Yao Fan, Feng Xie, Hang Zhou, Ke Jin, Li Shao, Wenhao Shi, Pengfei Fang, Bing Yang, Hans van Dam and 10 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

87 citing papers in PubMed, 183 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. OTU deubiquitinases in disease: roles and targeting.Trends in molecular medicine · 2026
    Review
  7. Review
  8. Article
  9. Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review

27 more citing papers are in PubMed but not listed here.

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

20 authors at 8 institutions in 3 countries.

Zhengkui ZhangLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Yao FanLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Feng XieInstitutes of Biology and Medical Science, Soochow University, 215123, Suzhou, China.
Hang ZhouLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Ke JinLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Li ShaoState Key Laboratory for Diagnostic and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, 310000, Hangzhou, China.
Wenhao ShiState Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 100039, Beijing, China.
Pengfei FangLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Bing YangDepartment of Pharmaceutical Chemistry and the Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, 94158, USA.
Hans van DamDepartment of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medical Center, Postbus 9600, 2300 RC, Leiden, The Netherlands.
Peter Ten DijkeDepartment of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medical Center, Postbus 9600, 2300 RC, Leiden, The Netherlands.
Xiaofeng ZhengDepartment of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.
Xiaohua YanTsinghua University, 100084, Beijing, China.
Junling JiaLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Min ZhengState Key Laboratory for Diagnostic and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, 310000, Hangzhou, China.
Jin JinLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Chen DingState Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 100039, Beijing, China.
Sheng YeLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Fangfang ZhouInstitutes of Biology and Medical Science, Soochow University, 215123, Suzhou, China.ORCID http://orcid.org/0000-0003-1870-7584
Long ZhangLife Sciences Institute and Innovation Center for Cell Signalling Network, Zhejiang University, Hangzhou, 310058, Zhejiang, China. L_Zhang@zju.edu.cn.ORCID http://orcid.org/0000-0001-8139-0474
Zhejiang University · CNFudan University · CNLeiden University Medical Center · NLSoochow University · CNThe University of Texas MD Anderson Cancer Center · USTsinghua University · CNUniversity of California, San Francisco · USZhejiang Lab · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metastasis is the main cause of death in cancer patients. TGF-β is pro-metastatic for malignant cancer cells. Here we report a loss-of-function screen in mice with metastasis as readout and identify OTUD1 as a metastasis-repressing factor. OTUD1-silenced cancer cells show mesenchymal and stem-cell-like characteristics. Further investigation reveals that OTUD1 directly deubiquitinates the TGF-β pathway inhibitor SMAD7 and prevents its degradation. Moreover, OTUD1 cleaves Lysine 33-linked poly-ubiquitin chains of SMAD7 Lysine 220, which exposes the SMAD7 PY motif, enabling SMURF2 binding and subsequent TβRI turnover at the cell surface. Importantly, OTUD1 is lost in multiple types of human cancers and loss of OTUD1 increases metastasis in intracardial xenograft and orthotopic transplantation models, and correlates with poor prognosis among breast cancer patients. High levels of OTUD1 inhibit cancer stemness and shut off metastasis. Thus, OTUD1 represses breast cancer metastasis by mitigating TGF-β-induced pro-oncogenic responses via deubiquitination of SMAD7.

Indexed as

UbiquitinationAnimalsBreast NeoplasmsCell LineCell Line, TumorDoxycyclineFemaleHEK293 CellsHumansMCF-7 CellsMice, Inbred BALB CMice, NudeNeoplasm MetastasisRNA InterferenceSmad7 ProteinUbiquitin-Specific ProteasesDoxycyclineOTUD1 protein, humanSmad7 ProteinUbiquitin-Specific Proteases

Identifiers

PMID29235476
PMCPMC5727433
OpenAlexW2773915736

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.