TY - JOUR TI - Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis AU - Nokin, Marie-Julie AU - Durieux, Florence AU - Peixoto, Paul AU - Chiavarina, Barbara AU - Peulen, Olivier AU - Blomme, Arnaud AU - Turtoi, Andrei AU - Costanza, Brunella AU - Smargiasso, Nicolas AU - Baiwir, Dominique AU - Scheijen, Jean L AU - Schalkwijk, Casper G AU - Leenders, Justine AU - De Tullio, Pascal AU - Bianchi, Elettra AU - Thiry, Marc AU - Uchida, Koji AU - Spiegel, David A AU - Cochrane, James R AU - Hutton, Craig A AU - De Pauw, Edwin AU - Delvenne, Philippe AU - Belpomme, Dominique AU - Castronovo, Vincent AU - Bellahcène, Akeila A2 - DeBerardinis, Ralph VL - 5 PY - 2016 DA - 2016/10/19 SP - e19375 C1 - eLife 2016;5:e19375 DO - 10.7554/eLife.19375 UR - https://doi.org/10.7554/eLife.19375 AB - 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. KW - carbonyl stress KW - glyoxalase 1 KW - LATS1 KW - breast cancer KW - methylglyoxal KW - YAP JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -