Evidence map›Paper›PMID 30544196›Full record

ArticleNucleic acids research2019

SMYD3 promotes the epithelial-mesenchymal transition in breast cancer.

Claudio Fenizia, Cinzia Bottino, Silvia Corbetta, Raffaella Fittipaldi, Pamela Floris, Germano Gaudenzi, Silvia Carra, Franco Cotelli, Giovanni Vitale, Giuseppina Caretti

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
3.3field-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

57 citing papers in PubMed, 94 citations in OpenAlex.

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  8. ZNF8 Orchestrates with Smad3 to Promote Lung Metastasis by Recruiting SMYD3 in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
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  10. Genetic Alterations ofInternational journal of molecular sciences · 2024
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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

10 authors at 2 institutions in 1 country.

Claudio FeniziaDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Cinzia BottinoDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Silvia CorbettaDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Raffaella FittipaldiDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Pamela FlorisDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Germano GaudenziLaboratory of Geriatric and Oncologic Neuroendocrinology Research, Istituto Auxologico Italiano IRCCS, Milan, Italy.
Silvia CarraLaboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy.
Franco CotelliDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Giovanni VitaleLaboratory of Geriatric and Oncologic Neuroendocrinology Research, Istituto Auxologico Italiano IRCCS, Milan, Italy.
Giuseppina CarettiDepartment of Biosciences, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
University of Milan · ITIRCCS Istituto Auxologico Italiano · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SMYD3 is a methylase previously linked to cancer cell invasion and migration. Here we show that SMYD3 favors TGFβ-induced epithelial-mesenchymal transition (EMT) in mammary epithelial cells, promoting mesenchymal and EMT transcription factors expression. SMYD3 directly interacts with SMAD3 but it is unnecessary for SMAD2/3 phosphorylation and nuclear translocation. Conversely, SMYD3 is indispensable for SMAD3 direct association to EMT genes regulatory regions. Accordingly, SMYD3 knockdown or its pharmacological blockade with the BCI121 inhibitor dramatically reduce TGFβ-induced SMAD3 association to the chromatin. Remarkably, BCI121 treatment attenuates mesenchymal genes transcription in the mesenchymal-like MDA-MB-231 cell line and reduces their invasive ability in vivo, in a zebrafish xenograft model. In addition, clinical datasets analysis revealed that higher SMYD3 levels are linked to a less favorable prognosis in claudin-low breast cancers and to a reduced metastasis free survival in breast cancer patients. Overall, our data point at SMYD3 as a pivotal SMAD3 cofactor that promotes TGFβ-dependent mesenchymal gene expression and cell migration in breast cancer, and support SMYD3 as a promising pharmacological target for anti-cancer therapy.

Indexed as

AnimalsBreast NeoplasmsCell Line, TumorCell MovementChromatinEpithelial-Mesenchymal TransitionFemaleGene Knockdown TechniquesHistone-Lysine N-MethyltransferaseHumansNeoplasm InvasivenessPhosphorylationSignal TransductionSmad3 ProteinTransforming Growth Factor betaXenograft Model Antitumor AssaysChromatinHistone-Lysine N-MethyltransferaseSmad3 ProteinSMAD3 protein, humanSMYD3 protein, humanTransforming Growth Factor beta

Identifiers

PMID30544196
PMCPMC6379668
OpenAlexW2904360942

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.