Evidence map›Paper›PMID 30341066›Full record

ArticleCancer research2019

TGFβ-Activated USP27X Deubiquitinase Regulates Cell Migration and Chemoresistance via Stabilization of Snail1.

Guillem Lambies, Martina Miceli, Catalina Martínez-Guillamon, Rubén Olivera-Salguero, Raúl Peña, Carolina-Paola Frías, Irene Calderón, Boyko S Atanassov, Sharon Y R Dent, Joaquín Arribas and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

71 citing papers in PubMed, 98 citations in OpenAlex.

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  13. Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025
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  19. Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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11 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

12 authors at 5 institutions in 2 countries.

Guillem LambiesPrograma de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Unidad Asociada CSIC, Barcelona, Spain.
Martina MiceliPrograma de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Unidad Asociada CSIC, Barcelona, Spain.
Catalina Martínez-GuillamonPrograma de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Unidad Asociada CSIC, Barcelona, Spain.ORCID 0000-0002-9879-4333
Rubén Olivera-SalgueroPrograma de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Unidad Asociada CSIC, Barcelona, Spain.
Raúl PeñaPrograma de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Unidad Asociada CSIC, Barcelona, Spain.
Carolina-Paola FríasPrograma de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Unidad Asociada CSIC, Barcelona, Spain.
Irene CalderónPrograma de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Unidad Asociada CSIC, Barcelona, Spain.
Boyko S AtanassovDepartment of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
Sharon Y R DentDepartment of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Smithville, Texas.ORCID 0000-0002-4824-3269
Joaquín ArribasPreclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO) CIBERONC, Barcelona, Spain.
Antonio García de HerrerosPrograma de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Unidad Asociada CSIC, Barcelona, Spain. victor.diaz@upf.edu agarcia@imim.es.
Víctor M DíazPrograma de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Unidad Asociada CSIC, Barcelona, Spain. victor.diaz@upf.edu agarcia@imim.es.ORCID 0000-0001-8561-7576
Hospital del Mar Research Institute · ESUniversitat Pompeu Fabra · ESInstitució Catalana de Recerca i Estudis Avançats · ESRoswell Park Comprehensive Cancer Center · USThe University of Texas MD Anderson Cancer Center · US

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MARK G FRATTINI · 1985 to 2026
$116.6M
NCI NIH HHS P30 CA016056
6 · The paper itself

Abstract

In cancer cells, epithelial-to-mesenchymal transition (EMT) is controlled by Snail1, a transcriptional factor also required for the activation of cancer-associated fibroblasts (CAF). Snail1 is short-lived in normal epithelial cells as a consequence of its coordinated and continuous ubiquitination by several F-box-specific E3 ligases, but its degradation is prevented in cancer cells and in activated fibroblasts. Here, we performed an siRNA screen and identified USP27X as a deubiquitinase that increases Snail1 stability. Expression of USP27X in breast and pancreatic cancer cell lines and tumors positively correlated with Snail1 expression levels. Accordingly, downregulation of USP27X decreased Snail1 protein in several tumor cell lines. USP27X depletion impaired Snail1-dependent cell migration and invasion and metastasis formation and increased cellular sensitivity to cisplatin. USP27X was upregulated by TGFβ during EMT and was required for TGFβ-induced expression of Snail1 and other mesenchymal markers in epithelial cells and CAF. In agreement with this, depletion of USP27X prevented TGFβ-induced EMT and fibroblast activation. Collectively, these results indicate that USP27X is an essential protein controlling Snail1 expression and function and may serve as a target for inhibition of Snail1-dependent tumoral invasion and chemoresistance. SIGNIFICANCE: These findings show that inhibition of USP27X destabilizes Snail1 to impair EMT and renders tumor cells sensitive to chemotherapy, thus opening new strategies for the inhibition of Snail1 expression and its protumoral actions.

Indexed as

Cell MovementDrug Resistance, NeoplasmAnimalsBreast NeoplasmsCancer-Associated FibroblastsEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansMiceMice, Inbred NODMice, SCIDNeoplasm InvasivenessProtein StabilityRNA, Small InterferingSnail Family Transcription FactorsRNA, Small InterferingSNAI1 protein, humanSnail Family Transcription FactorsTransforming Growth Factor betaUbiquitinUbiquitin-Specific ProteasesUSP27X protein, human

Identifiers

PMID30341066
PMCPMC9386731
OpenAlexW2897751391

What OpenQuestion holds

Textmetadata
LicenceTDM
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.