eLife (Oct 2016)
Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis
- Marie-Julie Nokin,
- Florence Durieux,
- Paul Peixoto,
- Barbara Chiavarina,
- Olivier Peulen,
- Arnaud Blomme,
- Andrei Turtoi,
- Brunella Costanza,
- Nicolas Smargiasso,
- Dominique Baiwir,
- Jean L Scheijen,
- Casper G Schalkwijk,
- Justine Leenders,
- Pascal De Tullio,
- Elettra Bianchi,
- Marc Thiry,
- Koji Uchida,
- David A Spiegel,
- James R Cochrane,
- Craig A Hutton,
- Edwin De Pauw,
- Philippe Delvenne,
- Dominique Belpomme,
- Vincent Castronovo,
- Akeila Bellahcène
Affiliations
- Marie-Julie Nokin
- Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
- Florence Durieux
- Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
- Paul Peixoto
- Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
- Barbara Chiavarina
- Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
- Olivier Peulen
- Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
- Arnaud Blomme
- Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
- Andrei Turtoi
- Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
- Brunella Costanza
- Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
- Nicolas Smargiasso
- Mass Spectrometry Laboratory, GIGA-Systems Biology and Chemical Biology, University of Liège, Liège, Belgium
- Dominique Baiwir
- GIGA Proteomic Facility, University of Liège, Liège, Belgium
- Jean L Scheijen
- Laboratory for Metabolism and Vascular Medicine, Department of Internal Medicine, Maastricht University, Maastricht, Netherlands
- Casper G Schalkwijk
- Laboratory for Metabolism and Vascular Medicine, Department of Internal Medicine, Maastricht University, Maastricht, Netherlands; Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands
- Justine Leenders
- Laboratory of Medicinal Chemistry - CIRM, University of Liège, Liège, Belgium
- Pascal De Tullio
- Laboratory of Medicinal Chemistry - CIRM, University of Liège, Liège, Belgium
- Elettra Bianchi
- Department of Pathology, CHU, University of Liège, Liège, Belgium
- Marc Thiry
- Laboratory of Cellular and Tissular Biology, GIGA-Neurosciences, University of Liège, Liège, Belgium
- Koji Uchida
- Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences, University of Nagoya, Nagoya, Japan
- David A Spiegel
- Department of Chemistry, Yale University, New Haven, United States
- James R Cochrane
- ORCiD
- School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia
- Craig A Hutton
- School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia
- Edwin De Pauw
- Mass Spectrometry Laboratory, GIGA-Systems Biology and Chemical Biology, University of Liège, Liège, Belgium
- Philippe Delvenne
- Department of Pathology, CHU, University of Liège, Liège, Belgium
- Dominique Belpomme
- Association for Research and Treatments Against Cancer, Paris, France
- Vincent Castronovo
- Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
- Akeila Bellahcène
- Metastasis Research Laboratory, GIGA-CANCER, University of Liège, Liège, Belgium
- DOI
- https://doi.org/10.7554/eLife.19375
- Journal volume & issue
-
Vol. 5
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.
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