Accéder au contenu
Merck

Aerobic glycolysis tunes YAP/TAZ transcriptional activity.

The EMBO journal (2015-03-23)
Elena Enzo, Giulia Santinon, Arianna Pocaterra, Mariaceleste Aragona, Silvia Bresolin, Mattia Forcato, Daniela Grifoni, Annalisa Pession, Francesca Zanconato, Giulia Guzzo, Silvio Bicciato, Sirio Dupont
RÉSUMÉ

Increased glucose metabolism and reprogramming toward aerobic glycolysis are a hallmark of cancer cells, meeting their metabolic needs for sustained cell proliferation. Metabolic reprogramming is usually considered as a downstream consequence of tumor development and oncogene activation; growing evidence indicates, however, that metabolism on its turn can support oncogenic signaling to foster tumor malignancy. Here, we explored how glucose metabolism regulates gene transcription and found an unexpected link with YAP/TAZ, key transcription factors regulating organ growth, tumor cell proliferation and aggressiveness. When cells actively incorporate glucose and route it through glycolysis, YAP/TAZ are fully active; when glucose metabolism is blocked, or glycolysis is reduced, YAP/TAZ transcriptional activity is decreased. Accordingly, glycolysis is required to sustain YAP/TAZ pro-tumorigenic functions, and YAP/TAZ are required for the full deployment of glucose growth-promoting activity. Mechanistically we found that phosphofructokinase (PFK1), the enzyme regulating the first committed step of glycolysis, binds the YAP/TAZ transcriptional cofactors TEADs and promotes their functional and biochemical cooperation with YAP/TAZ. Strikingly, this regulation is conserved in Drosophila, where phosphofructokinase is required for tissue overgrowth promoted by Yki, the fly homologue of YAP. Moreover, gene expression regulated by glucose metabolism in breast cancer cells is strongly associated in a large dataset of primary human mammary tumors with YAP/TAZ activation and with the progression toward more advanced and malignant stages. These findings suggest that aerobic glycolysis endows cancer cells with particular metabolic properties and at the same time sustains transcription factors with potent pro-tumorigenic activities such as YAP/TAZ.

MATÉRIAUX
Référence du produit
Marque
Description du produit

Sigma-Aldrich
Glycérol, for molecular biology, ≥99.0%
Sigma-Aldrich
Chlorure de sodium, for molecular biology, DNase, RNase, and protease, none detected, ≥99% (titration)
Sigma-Aldrich
Chlorure de magnésium, anhydrous, ≥98%
Sigma-Aldrich
Chlorure de magnésium solution, for molecular biology, 1.00 M±0.01 M
Sigma-Aldrich
Chlorure de sodium solution, 5 M in H2O, BioReagent, for molecular biology, suitable for cell culture
Sigma-Aldrich
Chlorure de sodium solution, 0.9% in water, BioXtra, suitable for cell culture
Sigma-Aldrich
Chlorure de sodium, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%
Sigma-Aldrich
2-Désoxy-D-glucose, ≥98% (GC), crystalline
Sigma-Aldrich
Tricine, ≥99% (titration)
SAFC
Chlorure de sodium solution, 5 M
Sigma-Aldrich
Glycérol solution, 83.5-89.5% (T)
Sigma-Aldrich
Acide éthylènediaminetétraacétique solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
D-(+)-galactose, ≥99% (HPLC), BioReagent, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Glycérol, BioUltra, for molecular biology, anhydrous, ≥99.5% (GC)
Sigma-Aldrich
Glycérol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)
Sigma-Aldrich
2-Désoxy-D-glucose, ≥99% (GC), crystalline
Sigma-Aldrich
Anticorps anti-glycéraldéhyde-3-phosphate déshydrogénase, clone 6C5, clone 6C5, Chemicon®, from mouse
Sigma-Aldrich
Chlorure de sodium, BioXtra, ≥99.5% (AT)
Sigma-Aldrich
Chlorure de magnésium, powder, <200 μm
Sigma-Aldrich
Chlorure de sodium solution, BioUltra, for molecular biology, ~5 M in H2O
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
Sigma-Aldrich
Chlorure de sodium, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
Glycérol, ≥99.5%
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Glycérol, FCC, FG
Sigma-Aldrich
Chlorure de sodium, 99.999% trace metals basis
Sigma-Aldrich
D-(+)-Mannose, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Désoxynivalénol
Sigma-Aldrich
Chlorure de magnésium solution, BioUltra, for molecular biology, 2 M in H2O