The oncogenic transcription factor c-Jun regulates glutaminase expression and sensitizes cells to glutaminase-targeted therapy

Lukey, M. J., Greene, K. S., Erickson, J. W., Wilson, K. F., Cerione, R. A. (April 2016) The oncogenic transcription factor c-Jun regulates glutaminase expression and sensitizes cells to glutaminase-targeted therapy. Nat Commun, 7. p. 11321. ISSN 2041-1723

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URL: https://www.ncbi.nlm.nih.gov/pubmed/27089238
DOI: 10.1038/ncomms11321

Abstract

Many transformed cells exhibit altered glucose metabolism and increased utilization of glutamine for anabolic and bioenergetic processes. These metabolic adaptations, which accompany tumorigenesis, are driven by oncogenic signals. Here we report that the transcription factor c-Jun, product of the proto-oncogene JUN, is a key regulator of mitochondrial glutaminase (GLS) levels. Activation of c-Jun downstream of oncogenic Rho GTPase signalling leads to elevated GLS gene expression and glutaminase activity. In human breast cancer cells, GLS protein levels and sensitivity to GLS inhibition correlate strongly with c-Jun levels. We show that c-Jun directly binds to the GLS promoter region, and is sufficient to increase gene expression. Furthermore, ectopic overexpression of c-Jun renders breast cancer cells dependent on GLS activity. These findings reveal a role for c-Jun as a driver of cancer cell metabolic reprogramming, and suggest that cancers overexpressing JUN may be especially sensitive to GLS-targeted therapies.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders > cancer > cancer types > breast cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > c-jun
organs, tissues, organelles, cell types and functions > organs types and functions > metabolism
CSHL Authors:
Communities: CSHL labs > Lukey lab
Depositing User: Adrian Gomez
Date: 18 April 2016
Date Deposited: 27 Jan 2020 19:51
Last Modified: 27 Jan 2020 19:51
PMCID: PMC4837472
Related URLs:
URI: https://repository.cshl.edu/id/eprint/38936

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