Evidence map›Paper›PMID 36646950›Full record

ArticleCellular and molecular life sciences : CMLS2023

Opposing USP19 splice variants in TGF-β signaling and TGF-β-induced epithelial-mesenchymal transition of breast cancer cells.

Jing Zhang, Maarten van Dinther, Midory Thorikay, Babak Mousavi Gourabi, Boudewijn P T Kruithof, Peter Ten Dijke

Open access · hybridAbstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

13 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025
    Review
  4. Article
  5. Review
  6. Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
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

6 authors at 1 institution in 1 country.

Jing ZhangOncode Institute, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.ORCID http://orcid.org/0000-0002-0137-6902
Maarten van DintherOncode Institute, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
Midory ThorikayOncode Institute, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
Babak Mousavi GourabiDepartment of Anatomy and Embryology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
Boudewijn P T KruithofDepartment of Cell Chemical Biology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
Peter Ten DijkeOncode Institute, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands. P.ten_Dijke@lumc.nl.ORCID http://orcid.org/0000-0002-7234-342X
Leiden University Medical Center · NL

Funding

Cancer Genomics Centre CGC.NLChinese Scholarship Council CSCZonMw 09120012010061
6 · The paper itself

Abstract

Ubiquitin-specific protease (USP)19 is a deubiquitinating enzyme that regulates the stability and function of multiple proteins, thereby controlling various biological responses. The alternative splicing of USP19 results in the expression of two major encoded variants that are localized to the endoplasmic reticulum (ER) (USP19-ER) and cytoplasm (USP19-CY). The importance of alternative splicing for the function of USP19 remains unclear. Here, we demonstrated that USP19-CY promotes TGF-β signaling by directly interacting with TGF-β type I receptor (TβRI) and protecting it from degradation at the plasma membrane. In contrast, USP19-ER binds to and sequesters TβRI in the ER. By decreasing cell surface TβRI levels, USP19-ER inhibits TGF-β/SMAD signaling in a deubiquitination-independent manner. Moreover, USP19-ER inhibits TGF-β-induced epithelial-mesenchymal transition (EMT), whereas USP19-CY enhances EMT, as well as the migration and extravasation of breast cancer cells. Furthermore, USP19-CY expression is correlated with poor prognosis and is higher in breast cancer tissues than in adjacent normal tissues. Notably, the splicing modulator herboxidiene inhibits USP19-CY, increases USP19-ER expression and suppresses breast cancer cell migration. Targeting USP19 splicing or its deubiquitinating activity may have potential therapeutic effects on breast cancer.

Indexed as

Breast NeoplasmsTransforming Growth Factor betaCell Line, TumorCell MembraneCell MovementEndopeptidasesEpithelial-Mesenchymal TransitionFemaleHumansReceptors, Transforming Growth Factor betaEndopeptidasesReceptors, Transforming Growth Factor betaTransforming Growth Factor betaUSP19 protein, humanAlternative spliced isoformBreast cancerEpithelial–mesenchymal transitionHerboxidieneTransforming growth factor-βUSP19

Identifiers

PMID36646950
PMCPMC9842591
OpenAlexW4316669854

What OpenQuestion holds

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LicenceCC BY
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 OpenQuestion graph.