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

Autor: Barbara Chiavarina, Brunella Costanza, Justine Leenders, Philippe Delvenne, Elettra Bianchi, James R. Cochrane, Koji Uchida, Pascal de Tullio, Paul Peixoto, Akeila Bellahcene, Craig A. Hutton, Olivier Peulen, Dominique Baiwir, Marc Thiry, Casper G. Schalkwijk, Vincent Castronovo, Andrei Turtoi, Dominique Belpomme, Arnaud Blomme, Florence Durieux, Jean L.J.M. Scheijen, Nicolas Smargiasso, Marie-Julie Nokin, Edwin De Pauw, David Spiegel
Přispěvatelé: Promovendi CD, Interne Geneeskunde, MUMC+: MA Alg Interne Geneeskunde (9), RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, Université de Liège, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Maastricht University [Maastricht], Cardiovascular Research Institute Maastricht (CARIM), Centre Hospitalier Universitaire de Liège (CHU-Liège), Nagoya University, Yale University [New Haven], University of Melbourne, Association for Research and Treatments Against Cancer (ARTAC)
Rok vydání: 2016
Předmět:
Glycation End Products
Advanced
0301 basic medicine
Glycosylation
Metastasis
chemistry.chemical_compound
Lactoylglutathione lyase
Glycation
cell biology
methylglyoxal
Neoplasm Metastasis
Biology (General)
cancer biology
General Neuroscience
MESH: Glycation End Products
Advanced
Methylglyoxal
General Medicine
Pyruvaldehyde
MESH: Glycosylation
Aerobiosis
LATS1
3. Good health
carbonyl stress
MESH: Glycolysis
Medicine
YAP
Glycolysis
Research Article
medicine.medical_specialty
MESH: Pyruvaldehyde
MESH: Cell Line
Tumor
QH301-705.5
Science
chicken
Breast Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
MESH: Phosphoproteins
glyoxalase 1
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
breast cancer
Cell Line
Tumor
MESH: Aerobiosis
MESH: Cell Proliferation
Internal medicine
MESH: HSP90 Heat-Shock Proteins
medicine
Humans
HSP90 Heat-Shock Proteins
human
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
mouse
Adaptor Proteins
Signal Transducing
Cell Proliferation
MESH: Adaptor Proteins
Signal Transducing
Hippo signaling pathway
MESH: Humans
General Immunology and Microbiology
YAP-Signaling Proteins
Phosphoproteins
medicine.disease
MESH: Neoplasm Metastasis
030104 developmental biology
Endocrinology
chemistry
Tumor progression
Anaerobic glycolysis
MESH: Protein Processing
Post-Translational
Cancer cell
biology.protein
Cancer research
Protein Processing
Post-Translational
MESH: Breast Neoplasms
Transcription Factors
Zdroj: Elife, 5:e19375. eLife Sciences Publications, Ltd
eLife
eLife, eLife Sciences Publication, 2016, 5, pp.e19375. ⟨10.7554/eLife.19375⟩
eLife, Vol 5 (2016)
ISSN: 2050-084X
Popis: 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. DOI: http://dx.doi.org/10.7554/eLife.19375.001
Databáze: OpenAIRE
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