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

• Published in: eLife Vol. 5
• Main Authors: Nokin, Marie-Julie, Durieux, Florence, Peixoto, Paul, Chiavarina, Barbara, Peulen, Olivier, Blomme, Arnaud, Turtoi, Andrei, Costanza, Brunella, Smargiasso, Nicolas, Baiwir, Dominique, Scheijen, Jean L, Schalkwijk, Casper G, Leenders, Justine, De Tullio, Pascal, Bianchi, Elettra, Thiry, Marc, Uchida, Koji, Spiegel, David A, Cochrane, James R, Hutton, Craig A, De Pauw, Edwin, Delvenne, Philippe, Belpomme, Dominique, Castronovo, Vincent, Bellahcène, Akeila
• Format: Journal Article Web Resource
• Language: English
• Published: England eLife Sciences Publications Ltd 19-10-2016; eLife Sciences Publication; eLife Sciences Publications; eLife Sciences Publications, Ltd
• Subjects: Adaptor Proteins, Signal Transducing; Adaptor Proteins, Signal Transducing - metabolism; Advanced glycosylation end products; Aerobiosis; Biochemistry; Biochemistry, biophysics & molecular biology; Biochemistry, Molecular Biology; Biochimie, biophysique & biologie moléculaire; Biology; Breast cancer; Breast Neoplasms; Breast Neoplasms - pathology; Breast Neoplasms - physiopathology; Cancer; Cancer Biology; Cancer therapies; carbonyl stress; Carnosine; Cell Biology; Cell Line, Tumor; Cell Proliferation; Chemistry; Diabetes; Experiments; Gene expression; Glycation End Products, Advanced; Glycation End Products, Advanced - metabolism; Glycolysis; Glycosylation; glyoxalase 1; HSP90 Heat-Shock Proteins; HSP90 Heat-Shock Proteins - metabolism; Hsp90 protein; Human health sciences; Humans; Hyperglycemia; Kinases; Laboratories; LATS1; Life Sciences; Localization; Medical research; Metabolism; Metabolites; Metastases; Metastasis; methylglyoxal; Neoplasm Metastasis; Oncologie; Oncology; Phosphoproteins; Phosphoproteins - metabolism; Protein Processing, Post-Translational; Proteins; Pyruvaldehyde; Pyruvaldehyde - metabolism; Sciences de la santé humaine; Sciences du vivant; Signal transduction; Statistical analysis; Transcription; Transcription Factors; Tumors; YAP; YAP-Signaling Proteins; Yes-associated protein; LATS1; methylglyoxal; mouse; chicken; cell biology; glyoxalase 1; YAP; breast cancer; cancer biology; carbonyl stress; human
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.19375

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.