Journal article

Response of BRAF-Mutant Melanoma to BRAF Inhibition Is Mediated by a Network of Transcriptional Regulators of Glycolysis

Tiffany J Parmenter, Margarete Kleinschmidt, Kathryn M Kinross, Simon T Bond, Jason Li, Mohan R Kaadige, Aparna Rao, Karen E Sheppard, Willy Hugo, Gulietta M Pupo, Richard B Pearson, Sean L Mcgee, Georgina V Long, Richard A Scolyer, Helen Rizos, Roger S Lo, Carleen Cullinane, Donald E Ayer, Antoni Ribas, Ricky W Johnstone Show all

CANCER DISCOVERY | AMER ASSOC CANCER RESEARCH | Published : 2014

Abstract

UNLABELLED: Deregulated glucose metabolism fulfills the energetic and biosynthetic requirements for tumor growth driven by oncogenes. Because inhibition of oncogenic BRAF causes profound reductions in glucose uptake and a strong clinical benefit in BRAF-mutant melanoma, we examined the role of energy metabolism in responses to BRAF inhibition. We observed pronounced and consistent decreases in glycolytic activity in BRAF-mutant melanoma cells. Moreover, we identified a network of BRAF-regulated transcription factors that control glycolysis in melanoma cells. Remarkably, this network of transcription factors, including hypoxia-inducible factor-1α, MYC, and MONDOA (MLXIP), drives glycolysis do..

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Awarded by NCI


Awarded by NIH


Awarded by National Health and Medical Research Council (NHMRC) Career Development Fellowship


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Funding Acknowledgements

This work was supported by grants from the National Health and Medical Research Council of Australia (to R.J. Hicks, A. Rao, R. A. Scolyer, and G. A. McArthur), Cancer Council Victoria (to R.J. Hicks and G. A. McArthur), the Cancer Institute New South Wales (to R. A. Scolyer, H. Rizos, and G. V. Long), NCI K22CA151638 and 1P01CA168585 (to R. S. Lo) and NIH R01055668 (to D. E. Ayer). G. A. McArthur was a recipient of the Sir Edward Dunlop Fellowship of the Cancer Council of Victoria. S. L. McGee is supported by a National Health and Medical Research Council (NHMRC) Career Development Fellowship (APP1030474).