Evidence map›Paper›PMID 34231077›Full record

ArticleBreast cancer research and treatment2021

ZEB2 regulates endocrine therapy sensitivity and metastasis in luminal a breast cancer cells through a non-canonical mechanism.

Hope E Burks, Margarite D Matossian, Lyndsay Vanhoy Rhodes, Theresa Phamduy, Steven Elliott, Aaron Buechlein, Douglas B Rusch, David F B Miller, Kenneth P Nephew, Douglas Chrisey and 2 more

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Article in Breast cancer research and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 25% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
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  4. Article
  5. Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024
    Review
  6. Article
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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

12 authors at 3 institutions in 1 country.

Hope E Burks *Department of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.
Margarite D Matossian *Department of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.ORCID http://orcid.org/0000-0002-9527-1043
Lyndsay Vanhoy RhodesFlorida Gulf Coast University, Fort Myers, FL, 33965, USA.
Theresa PhamduyDepartment of Physics, Tulane University, New Orleans, LA, 70112, USA.
Steven ElliottDepartment of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.
Aaron BuechleinCenter of Genomics and Bioinformatics, Indiana University, Bloomington, IN, 47405, USA.
Douglas B RuschCenter of Genomics and Bioinformatics, Indiana University, Bloomington, IN, 47405, USA.
David F B MillerCenter of Genomics and Bioinformatics, Indiana University, Bloomington, IN, 47405, USA.
Kenneth P NephewMedical Sciences Program, Indiana University School of Medicine, Bloomington, IN, 47405, USA.
Douglas ChriseyDepartment of Physics, Tulane University, New Orleans, LA, 70112, USA.
Bridgette M Collins-BurowDepartment of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.
Matthew E BurowDepartment of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA. mburow@tulane.edu.
Tulane University · USIndiana University Bloomington · USFlorida Gulf Coast University · US

Funding

Foundation for the National Institutes of Health R01-CA125806-02Foundation for the National Institutes of Health R01-CA174785-01A1
6 · The paper itself

Abstract

purposeThe transcription factors ZEB1 and ZEB2 mediate epithelial-to-mesenchymal transition (EMT) and metastatic progression in numerous malignancies including breast cancer. ZEB1 and ZEB2 drive EMT through transcriptional repression of cell-cell junction proteins and members of the tumor suppressive miR200 family. However, in estrogen receptor positive (ER +) breast cancer, the role of ZEB2 as an independent driver of metastasis has not been fully investigated.

methodsIn the current study, we induced exogenous expression of ZEB2 in ER + MCF-7 and ZR-75-1 breast cancer cell lines and examined EMT gene expression and metastasis using dose-response qRT-PCR, transwell migration assays, proliferation assays with immunofluorescence of Ki-67 staining. We used RNA sequencing to identify pathways and genes affected by ZEB2 overexpression. Finally, we treated ZEB2-overexpressing cells with 17β-estradiol (E2) or ICI 182,780 to evaluate how ZEB2 affects estrogen response.

resultsContrary to expectation, we found that ZEB2 did not increase canonical epithelial nor decrease mesenchymal gene expressions. Furthermore, ZEB2 overexpression did not promote a mesenchymal cell morphology. However, ZEB1 and ZEB2 protein expression induced significant migration of MCF-7 and ZR-75-1 breast cancer cells in vitro and MCF-7 xenograft metastasis in vivo. Transcriptomic (RNA sequencing) pathway analysis revealed alterations in estrogen signaling regulators and pathways, suggesting a role for ZEB2 in endocrine sensitivity in luminal A breast cancer. Expression of ZEB2 was negatively correlated with estrogen receptor complex genes in luminal A patient tumors. Furthermore, treatment with 17β-estradiol (E2) or the estrogen receptor antagonist ICI 182,780 had no effect on growth of ZEB2-overexpressing cells.

conclusionZEB2 is a multi-functional regulator of drug sensitivity, cell migration, and metastasis in ER + breast cancer and functions through non-canonical mechanisms.

Indexed as

Breast NeoplasmsEpithelial-Mesenchymal TransitionZinc Finger E-box Binding Homeobox 2Cell Line, TumorCell MovementFemaleFulvestrantGene Expression Regulation, NeoplasticHumansMCF-7 CellsFulvestrantZEB2 protein, humanZinc Finger E-box Binding Homeobox 2Breast cancerEndocrine therapy resistanceEstrogenGene regulationLuminal AMetastasisZEB2

Identifiers

PMID34231077
OpenAlexW3154056720

What OpenQuestion holds

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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.