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

• DOI: 10.1038/ncomms11321
• Publication Date: 2016-04-18T12:50:58Z
• Authors: Michael J. Lukey; Kai Su Greene; Jon W. Erickson; Kristin F. Wilson; Richard A. Cerione
• Keywords: Glutaminase; c-jun; Ectopic expression; Proto-Oncogene Proteins c-myc

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