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Heat Shock Factor 1 (HSF1) cooperates with estrogen receptor α (ERα) in the regulation of estrogen action in breast cancer cells

  1. Natalia Vydra  Is a corresponding author
  2. Patryk Janus
  3. Paweł Kuś
  4. Tomasz Stokowy
  5. Katarzyna Mrowiec
  6. Agnieszka Toma-Jonik
  7. Aleksandra Krzywon
  8. Alexander Jorge Cortez
  9. Bartosz Wojtaś
  10. Bartłomiej Gielniewski
  11. Roman Jaksik
  12. Marek Kimmel
  13. Wieslawa Widlak  Is a corresponding author
  1. Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland
  2. Silesian University of Technology, Poland
  3. University of Bergen, Norway
  4. Polish Academy of Sciences, Poland
  5. Rice University, United States
Research Article
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Cite this article as: eLife 2021;10:e69843 doi: 10.7554/eLife.69843

Abstract

Heat shock factor 1 (HSF1), a key regulator of transcriptional responses to proteotoxic stress, was linked to estrogen (E2) signaling through estrogen receptor α (ERα). We found that an HSF1 deficiency may decrease ERα level, attenuate the mitogenic action of E2, counteract E2-stimulated cell scattering, and reduce adhesion to collagens and cell motility in ER-positive breast cancer cells. The stimulatory effect of E2 on the transcriptome is largely weaker in HSF1-deficient cells, in part due to the higher basal expression of E2-dependent genes, which correlates with the enhanced binding of unliganded ERα to chromatin in such cells. HSF1 and ERα can cooperate directly in E2-stimulated regulation of transcription, and HSF1 potentiates the action of ERα through a mechanism involving chromatin reorganization. Furthermore, HSF1 deficiency may increase the sensitivity to hormonal therapy (4-hydroxytamoxifen) or CDK4/6 inhibitors (palbociclib). Analyses of data from the TCGA database indicate that HSF1 increases the transcriptome disparity in ER-positive breast cancer and can enhance the genomic action of ERα. Moreover, only in ER-positive cancers, an elevated HSF1 level is associated with metastatic disease.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE159802, GSE159724 (scheduled to be released on Oct 21, 2021), and GSE186004 (scheduled to be released on Oct 13, 2022).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Natalia Vydra

    Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
    For correspondence
    natalia.vydra@io.gliwice.pl
    Competing interests
    The authors declare that no competing interests exist.
  2. Patryk Janus

    Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
    Competing interests
    The authors declare that no competing interests exist.
  3. Paweł Kuś

    Department of Systems Biology and Engineering, Silesian University of Technology, Gliwice, Poland
    Competing interests
    The authors declare that no competing interests exist.
  4. Tomasz Stokowy

    Department of Clinical Science, University of Bergen, Bergen, Norway
    Competing interests
    The authors declare that no competing interests exist.
  5. Katarzyna Mrowiec

    Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
    Competing interests
    The authors declare that no competing interests exist.
  6. Agnieszka Toma-Jonik

    Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
    Competing interests
    The authors declare that no competing interests exist.
  7. Aleksandra Krzywon

    Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4796-5478
  8. Alexander Jorge Cortez

    Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1284-2638
  9. Bartosz Wojtaś

    Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  10. Bartłomiej Gielniewski

    Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
    Competing interests
    The authors declare that no competing interests exist.
  11. Roman Jaksik

    Department of Systems Biology and Engineering, Silesian University of Technology, Gliwice, Poland
    Competing interests
    The authors declare that no competing interests exist.
  12. Marek Kimmel

    Department of Statistics, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Wieslawa Widlak

    Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
    For correspondence
    wieslawa.widlak@io.gliwice.pl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8440-9414

Funding

National Science Centre, Poland (2014/13/B/NZ7/02341)

  • Natalia Vydra

National Science Centre, Poland (2015/17/B/NZ3/03760)

  • Wieslawa Widlak

National Science Centre, Poland (2018/29/B/ST7/02550)

  • Marek Kimmel

European Social Fund (POWR.03.02.00-00-I029)

  • Paweł Kuś

European Social Fund (POWR.03.02.00-00-I029)

  • Alexander Jorge Cortez

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Maureen E Murphy, The Wistar Institute, United States

Publication history

  1. Received: April 28, 2021
  2. Accepted: November 15, 2021
  3. Accepted Manuscript published: November 16, 2021 (version 1)

Copyright

© 2021, Vydra et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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