Evidence map›Paper›PMID 28337662›Full record

ArticleBreast cancer research and treatment2017

A83-01 inhibits TGF-β-induced upregulation of Wnt3 and epithelial to mesenchymal transition in HER2-overexpressing breast cancer cells.

Yanyuan Wu, Trinh Tran, Sami Dwabe, Marianna Sarkissyan, Juri Kim, Miguel Nava, Sheilah Clayton, Richard Pietras, Robin Farias-Eisner, Jaydutt V Vadgama

RetractedOpen access · hybridAbstract readRetracted Publication
In one paragraph

Article in Breast cancer research and treatment, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.2field-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

33 citing papers in PubMed, 58 citations in OpenAlex.

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  16. Wnt/β-catenin signaling in cancers and targeted therapies.Signal transduction and targeted therapy · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Yanyuan WuDivision of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 90059, USA. yanyuanwu@cdrewu.edu.
Trinh TranDivision of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 90059, USA.
Sami DwabeDivision of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 90059, USA.
Marianna SarkissyanDivision of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 90059, USA.
Juri KimDivision of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 90059, USA.
Miguel NavaDivision of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 90059, USA.
Sheilah ClaytonDivision of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 90059, USA.
Richard PietrasDivision of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 90059, USA.
Robin Farias-EisnerDivision of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 90059, USA.
Jaydutt V VadgamaDivision of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 90059, USA.
Charles R. Drew University of Medicine and Science · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
Sustaining Faculty Development & Community EngagementS21MD000103 · NIMHD · CHARLES R. DREW UNIVERSITY OF MED &SCI · PI CARLISLE, DAVID M · 2001 to 2015
$73.9M
Workshop for Junior Biostatisticians in Health ResearchU54MD007598 · NIMHD · CHARLES R. DREW UNIVERSITY OF MED & SCI · PI Jaydutt V. Vadgama · 2012 to 2026
$60.0M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Supporting African American Churches to Promote Cancer ScreeningU54CA143931 · NCI · CHARLES R. DREW UNIVERSITY OF MED & SCI · PI VADGAMA, JAYDUTT V. · 2009 to 2022
$19.7M
The CDU-Clinical Research Education and Career Development ProgramR25MD007610 · NIMHD · CHARLES R. DREW UNIVERSITY OF MED & SCI · PI Roberto Balbino Vargas · 2012 to 2026
$7.8M
Training and Mentoring ProgramsU54CA143930 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PIETRAS, RICHARD JOSEPH · 2009 to 2020
$7.5M
Drew/UCLA Cancer Partnership ProgramU56CA101599 · NCI · CHARLES R. DREW UNIVERSITY OF MED &SCI · PI VADGAMA, JAYDUTT V. · 2003 to 2009
$1.3M
Charles R. Drew Student Scholar ProgramR25DK067015 · NIDDK · CHARLES R. DREW UNIVERSITY OF MED &SCI · PI VADGAMA, JAYDUTT V · 2003 to 2007
$226k
NCATS NIH HHS UL1 TR000124NCI NIH HHS N01 CA015083NCI NIH HHS P30 CA015083NCI NIH HHS U54 CA143930NCI NIH HHS U54 CA143931NCI NIH HHS U56 CA101599NIDDK NIH HHS R25 DK067015NIMHD NIH HHS R25 MD007610NIMHD NIH HHS S21 MD000103NIMHD NIH HHS U54 MD007598
6 · The paper itself

Abstract

purposeThe aim of this study is to investigate the mechanisms of interactions between TGF-β and Wnt/β-catenin pathways that induce and regulate EMT and promote breast cancer cells to become resistant to treatment.

methodsThe effect of TGF-β on Wnt/β-catenin signaling pathway was examined by using a human Wnt/β-catenin-regulated cDNA plate array and western blot analysis. The interaction of Twist at promoter of Wnt3 was examined by chromatin immunoprecipitation (ChIP) assay. Secreted Wnt3 level was determined by ELISA assay.

resultsHER2-overexpressing breast cancer cells treated with TGF-β have a reduced response to trastuzumab and exhibited EMT-like phenotype. The TGF-β-induced EMT in HER2-cells was concordant with upregulation of Wnt3 and β-catenin pathways. The TGF-β-induced induction of Wnt3 during EMT was found to be Smad3-dependent. ChIP analysis identified occupancy of Twist at promoter region of Wnt3. Knock-down of Twist by shRNA confirmed the significance of Twist in response to TGF-β regulating Wnt3 during EMT. Subsequently, TGF-β-induced matrix metalloproteinases, MMP1, MMP7, MMP9, MMP26, Vascular endothelial growth factors (VEGF), and activation of Wnt/β-catenin signaling were repressed by the shRNA treatment. TGF-βR1 ALK5 kinase inhibitor, A83-01 can effectively prevent the TGF-β-induced Twist and Wnt3. Co-treating A83-01 and trastuzumab inhibited TGF-β-induced cell invasion significantly in both trastuzumab responsive and resistant cells.

conclusionsOur data demonstrated an important interdependence between TGF-β and Wnt/β-catenin pathways inducing EMT in HER2-overexpressing breast cancer cells. Twist served as a linkage between the two pathways during TGF-β-induced EMT. A83-01 could inhibit the TGF-β-initiated pathway interactions and enhance HER2-cells response to trastuzumab treatment.

Indexed as

beta CateninBreast NeoplasmsCell Line, TumorDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionErb-b2 Receptor Tyrosine KinasesFemaleGene Expression Regulation, NeoplasticHumansProtein Serine-Threonine KinasesPyrazolesReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type IThiosemicarbazonesTransforming Growth Factor betaTrastuzumabA-83-01beta CateninCTNNB1 protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesProtein Serine-Threonine KinasesPyrazolesReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type ITGFBR1 protein, humanThiosemicarbazonesTransforming Growth Factor betaTrastuzumabTwist-Related Protein 1Vascular Endothelial Growth Factor AVEGFA protein, humanWnt3 ProteinWNT3 protein, humanEMTSmad3TGF-βTwistWnt3

Identifiers

PMID28337662
PMCPMC5427117
OpenAlexW2601738726

What OpenQuestion holds

Textmetadata
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.