Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis

  1. Marie-Julie Nokin
  2. Florence Durieux
  3. Paul Peixoto
  4. Barbara Chiavarina
  5. Olivier Peulen
  6. Arnaud Blomme
  7. Andrei Turtoi
  8. Brunella Costanza
  9. Nicolas Smargiasso
  10. Dominique Baiwir
  11. Jean L Scheijen
  12. Casper G Schalkwijk
  13. Justine Leenders
  14. Pascal De Tullio
  15. Elettra Bianchi
  16. Marc Thiry
  17. Koji Uchida
  18. David A Spiegel
  19. James R Cochrane
  20. Craig A Hutton
  21. Edwin De Pauw
  22. Philippe Delvenne
  23. Dominique Belpomme
  24. Vincent Castronovo
  25. Akeila Bellahcène  Is a corresponding author
  1. University of Liège, Belgium
  2. Maastricht University, Netherlands
  3. University of Nagoya, Japan
  4. Yale University, United States
  5. University of Melbourne, Australia
  6. Université de Liège, Belgium
  7. University of LIège, Belgium
  8. Association for Research and Treatments Against Cancer, France

Abstract

Metabolic reprogramming toward aerobic glycolysis unavoidably induces methylglyoxal (MG) formation in cancer cells. MG mediates the glycation of proteins to form advanced glycation end products (AGEs). We have recently demonstrated that MG-induced AGEs are a common feature of breast cancer. Little is known regarding the impact of MG-mediated carbonyl stress on tumor progression. Breast tumors with MG stress presented with high nuclear YAP, a key transcriptional co-activator regulating tumor growth and invasion. Elevated MG levels resulted in sustained YAP nuclear localization/activity that could be reverted using Carnosine, a scavenger for MG. MG treatment affected Hsp90 chaperone activity and decreased its binding to LATS1, a key kinase of the Hippo pathway. Cancer cells with high MG stress showed enhanced growth and metastatic potential in vivo. These findings reinforce the cumulative evidence pointing to hyperglycemia as a risk factor for cancer incidence and bring renewed interest in MG scavengers for cancer treatment.

Data availability

The following previously published data sets were used

Article and author information

Author details

  1. Marie-Julie Nokin

    Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  2. Florence Durieux

    Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  3. Paul Peixoto

    Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  4. Barbara Chiavarina

    Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  5. Olivier Peulen

    Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  6. Arnaud Blomme

    Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  7. Andrei Turtoi

    Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  8. Brunella Costanza

    Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  9. Nicolas Smargiasso

    Mass Spectrometry Laboratory, GIGA-Systems Biology and Chemical Biology, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  10. Dominique Baiwir

    GIGA Proteomic Facility, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  11. Jean L Scheijen

    Laboratory for Metabolism and Vascular Medicine, Department of Internal Medicine, Maastricht University, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  12. Casper G Schalkwijk

    Laboratory for Metabolism and Vascular Medicine, Department of Internal Medicine, Maastricht University, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  13. Justine Leenders

    Laboratory of Medicinal Chemistry - Center for Interdisciplinary Research on Medicines, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  14. Pascal De Tullio

    Laboratory of Medicinal Chemistry - Center for Interdisciplinary Research on Medicines, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  15. Elettra Bianchi

    Department of Pathology, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  16. Marc Thiry

    Laboratory of Cellular and Tissular Biology, GIGA-Neurosciences, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  17. Koji Uchida

    Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences, University of Nagoya, Nagoya, Japan
    Competing interests
    The authors declare that no competing interests exist.
  18. David A Spiegel

    Department of Chemistry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  19. James R Cochrane

    School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8796-2143
  20. Craig A Hutton

    School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  21. Edwin De Pauw

    Mass Spectrometry Laboratory, GIGA-Systems Biology and Chemical Biology, Université de Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  22. Philippe Delvenne

    Department of Pathology, Centre Hospitalier Universitaire de Liège, University of LIège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  23. Dominique Belpomme

    Association for Research and Treatments Against Cancer, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  24. Vincent Castronovo

    Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  25. Akeila Bellahcène

    Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
    For correspondence
    a.bellahcene@ulg.ac.be
    Competing interests
    The authors declare that no competing interests exist.

Funding

Université de Liège

  • Akeila Bellahcène

MJN, FD and BCo are Télévie Fellows, BCh, ABl and AT are Télévie Post-Doctoral Fellows, PDT and ABe are Senior Research Associates, all from the National Fund for Scientific Research (FNRS, Belgium). This work was also supported by the Centre Anti-Cancéreux, University of Liège, Belgium.The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Ralph DeBerardinis, UT Southwestern Medical Center, United States

Ethics

Animal experimentation: All animal experimental procedures were performed according to the Federation of European Laboratory Animal Sciences Associations (FELASA) and were reviewed and approved by the Institutional Animal Care and Ethics Committee of the University of Liege, Belgium (#14-1714). All surgery was performed under ketamin/xylazine anesthesia, and every effort was made to minimize suffering.

Human subjects: Human breast tumor tissues were obtained from the Pathology Department of the University Hospital of Liege in agreement with ethical guidelines of the University of Liege, Belgium (#2015-155).

Version history

  1. Received: July 4, 2016
  2. Accepted: October 17, 2016
  3. Accepted Manuscript published: October 19, 2016 (version 1)
  4. Version of Record published: October 26, 2016 (version 2)
  5. Version of Record updated: February 6, 2024 (version 3)

Copyright

© 2016, Nokin 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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  1. Marie-Julie Nokin
  2. Florence Durieux
  3. Paul Peixoto
  4. Barbara Chiavarina
  5. Olivier Peulen
  6. Arnaud Blomme
  7. Andrei Turtoi
  8. Brunella Costanza
  9. Nicolas Smargiasso
  10. Dominique Baiwir
  11. Jean L Scheijen
  12. Casper G Schalkwijk
  13. Justine Leenders
  14. Pascal De Tullio
  15. Elettra Bianchi
  16. Marc Thiry
  17. Koji Uchida
  18. David A Spiegel
  19. James R Cochrane
  20. Craig A Hutton
  21. Edwin De Pauw
  22. Philippe Delvenne
  23. Dominique Belpomme
  24. Vincent Castronovo
  25. Akeila Bellahcène
(2016)
Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis
eLife 5:e19375.
https://doi.org/10.7554/eLife.19375

Share this article

https://doi.org/10.7554/eLife.19375

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