Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citations
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Research
Cancer Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citations
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Research Article

EMT transcription factor ZEB1 represses the mutagenic POLθ-mediated end-joining pathway in breast cancers

Mélanie K. Prodhomme, Roxane M. Pommier, Camille Franchet, Frederique Fauvet, valerie bergoglio, Pierre Brousset, Anne-Pierre Morel, Anne-Cecile Brunac, Mojgan Devouassoux-Shisheboran, Virginie Petrilli, Caroline Moyret-Lalle, Jean-Sébastien Hoffmann, Alain Puisieux and Agnès Tissier
Mélanie K. Prodhomme
1Cancer Plasticity, Cancer Center of Lyon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roxane M. Pommier
2INSERM U1052 CNRS UMR5286 Centre de Recherche en Cancérologie de Lyon, INSERM-CNRS
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Roxane M. Pommier
Camille Franchet
3Department of Medical Oncology, Institut Claudius Regaud
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frederique Fauvet
4UMR, Inserm 1052 CNRS 52856, Cancer Research Center of Lyon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
valerie bergoglio
5Cancer Research Center of Toulouse, Inserm U1037, CNRS ERL5294, University of Toulouse
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for valerie bergoglio
Pierre Brousset
6Pathology, Institut Universitaire du cancer de Toulouse, Labex TOUCAN
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Pierre Brousset
Anne-Pierre Morel
7Centre Léon Bérard, Lyon, F-69008, France, Cancerology Research Center of Lyon, INSERM U1052/CNRS UMR 5286
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne-Cecile Brunac
3Department of Medical Oncology, Institut Claudius Regaud
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Anne-Cecile Brunac
Mojgan Devouassoux-Shisheboran
8Service d'Anatomie et Cytologie pathologiques, Hôpital de la Croix-Rousse
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Virginie Petrilli
9Cancer Center of Lyon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Caroline Moyret-Lalle
10UMR INSERM 1052 - CNRS 5286, Cancer Research Center of Lyon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Sébastien Hoffmann
11Laboratoire d'Excellence Toulouse Cancer (TOUCAN), Laboratoire de pathologie, Institut Universitaire du Cancer-Toulouse, Oncopole
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jean-Sébastien Hoffmann
Alain Puisieux
4UMR, Inserm 1052 CNRS 52856, Cancer Research Center of Lyon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Agnès Tissier
1Cancer Plasticity, Cancer Center of Lyon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Agnès Tissier
  • For correspondence: agnes.tissier@inserm.fr
DOI: 10.1158/0008-5472.CAN-20-2626
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

A characteristic of cancer development is the acquisition of genomic instability, which results from the inaccurate repair of DNA damage. Among double-strand break repair mechanisms induced by oncogenic stress, the highly mutagenic theta-mediated end joining (TMEJ) pathway, which requires DNA polymerase theta (POLθ) encoded by the POLQ gene, has been shown to be overexpressed in several human cancers. However, little is known regarding the regulatory mechanisms of TMEJ and the consequence of its dysregulation. In this study, we combine a bioinformatics approach exploring both METABRIC and TCGA databases with CRISPR/Cas9-mediated depletion of the zinc finger E-box binding homeobox 1 (ZEB1) in claudin-low tumor cells or forced expression of ZEB1 in basal-like tumor cells, two triple-negative breast cancer (TNBC) subtypes, to demonstrate that ZEB1 represses POLQ expression. ZEB1, a master EMT inducing-transcription factor, interacted directly with the POLQ promoter. Moreover, downregulation of POLQ by ZEB1 fostered micronuclei formation in TNBC tumor cell lines. Consequently, ZEB1 expression prevented TMEJ activity, with a major impact on genome integrity. In conclusion, we showed that ZEB1 directly inhibits the expression of POLQ and therefore TMEJ activity, controlling both stability and integrity of breast cancer cell genomes.

  • Received August 2, 2020.
  • Revision received October 12, 2020.
  • Accepted November 20, 2020.
  • Copyright ©2020, American Association for Cancer Research.

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

This OnlineFirst version was published on November 25, 2020
doi: 10.1158/0008-5472.CAN-20-2626

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
EMT transcription factor ZEB1 represses the mutagenic POLθ-mediated end-joining pathway in breast cancers
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
EMT transcription factor ZEB1 represses the mutagenic POLθ-mediated end-joining pathway in breast cancers
Mélanie K. Prodhomme, Roxane M. Pommier, Camille Franchet, Frederique Fauvet, valerie bergoglio, Pierre Brousset, Anne-Pierre Morel, Anne-Cecile Brunac, Mojgan Devouassoux-Shisheboran, Virginie Petrilli, Caroline Moyret-Lalle, Jean-Sébastien Hoffmann, Alain Puisieux and Agnès Tissier
Cancer Res November 25 2020 DOI: 10.1158/0008-5472.CAN-20-2626

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
EMT transcription factor ZEB1 represses the mutagenic POLθ-mediated end-joining pathway in breast cancers
Mélanie K. Prodhomme, Roxane M. Pommier, Camille Franchet, Frederique Fauvet, valerie bergoglio, Pierre Brousset, Anne-Pierre Morel, Anne-Cecile Brunac, Mojgan Devouassoux-Shisheboran, Virginie Petrilli, Caroline Moyret-Lalle, Jean-Sébastien Hoffmann, Alain Puisieux and Agnès Tissier
Cancer Res November 25 2020 DOI: 10.1158/0008-5472.CAN-20-2626
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Hypomorphic germline mutant p53 mouse model
  • ALK/N-Myc-driven NEPC via activating Wnt/β-catenin signaling
  • MetAP2 PET imaging for prostate cancer risk stratification
Show more Research Article
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement