Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Epithelial-mesenchymal plasticity determines estrogen receptor positive (ER+) breast cancer dormancy and reacquisition of an epithelial state drives awakening

Patrick Aouad, Yueyun Zhang, Céline Stibolt, Sendurai A. Mani, George Sflomos, View ORCID ProfileCathrin Brisken
doi: https://doi.org/10.1101/2021.07.22.453458
Patrick Aouad
1ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yueyun Zhang
1ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Céline Stibolt
1ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sendurai A. Mani
2Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas 77030
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
George Sflomos
1ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cathrin Brisken
1ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
3The Breast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Cathrin Brisken
  • For correspondence: cathrin.brisken@epfl.ch
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Estrogen receptor α-positive (ER+) breast cancers (BCs) represent more than 70% of all breast cancers and pose a particular clinical challenge because they recur up to decades after initial diagnosis and treatment. The mechanisms governing tumor cell dormancy and latent disease remain elusive due to a lack of adequate models. Here, we compare tumor progression of ER+ and triple-negative (TN) BC subtypes with a clinically relevant mouse intraductal xenografting approach (MIND). Both ER+ and TN BC cells disseminate already during the in situstage. However, TN disseminated tumor cells (DTCs) proliferate at the same rate as cells at the primary site and give rise to macro-metastases. ER+ DTCs have low proliferative indices, form only micro-metastases and lose epithelial characteristics. Expression of CDH1 is decreased whereas the mesenchymal marker VIM and the transcription factors, ZEB1/ZEB2, which control epithelial-mesenchymal plasticity (EMP) are increased. EMP is not detected earlier during ER+ BC development and not required for invasion or metastasis. In vivo, forced transition to the epithelial state through ectopic E-cadherin expression overcomes dormancy with increased growth of lung metastases. We conclude that EMP is essential for the generation of a dormant cell state and the development of latent disease. Targeting exit from EMP is of therapeutic potential.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted July 26, 2021.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Epithelial-mesenchymal plasticity determines estrogen receptor positive (ER+) breast cancer dormancy and reacquisition of an epithelial state drives awakening
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Epithelial-mesenchymal plasticity determines estrogen receptor positive (ER+) breast cancer dormancy and reacquisition of an epithelial state drives awakening
Patrick Aouad, Yueyun Zhang, Céline Stibolt, Sendurai A. Mani, George Sflomos, Cathrin Brisken
bioRxiv 2021.07.22.453458; doi: https://doi.org/10.1101/2021.07.22.453458
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Epithelial-mesenchymal plasticity determines estrogen receptor positive (ER+) breast cancer dormancy and reacquisition of an epithelial state drives awakening
Patrick Aouad, Yueyun Zhang, Céline Stibolt, Sendurai A. Mani, George Sflomos, Cathrin Brisken
bioRxiv 2021.07.22.453458; doi: https://doi.org/10.1101/2021.07.22.453458

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cancer Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3607)
  • Biochemistry (7581)
  • Bioengineering (5529)
  • Bioinformatics (20808)
  • Biophysics (10336)
  • Cancer Biology (7986)
  • Cell Biology (11645)
  • Clinical Trials (138)
  • Developmental Biology (6611)
  • Ecology (10214)
  • Epidemiology (2065)
  • Evolutionary Biology (13627)
  • Genetics (9550)
  • Genomics (12852)
  • Immunology (7925)
  • Microbiology (19553)
  • Molecular Biology (7668)
  • Neuroscience (42132)
  • Paleontology (308)
  • Pathology (1258)
  • Pharmacology and Toxicology (2203)
  • Physiology (3268)
  • Plant Biology (7045)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1951)
  • Systems Biology (5428)
  • Zoology (1118)