Journal article

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, Brunelle 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 Show all



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 a..

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University of Melbourne Researchers


Funding Acknowledgements

[ "Universite de Liege Akeila Bellahcene", "MJN, FD and BCo are Televie Fellows, BCh, ABI and AT are Televie 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-Cancereux, University of Liege, Belgium. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication." ]