Mitochondrial p32 is upregulated in Myc expressing brain cancers and mediates glutamine addiction
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Valentina Fogal1,*, Ivan Babic1,*, Ying Chao1, Sandra Pastorino1, Rajesh Mukthavaram1, Pengfei Jiang1, Yoon-Jae Cho3, Sandeep C. Pingle1, John R. Crawford1,2, David E. Piccioni1,2, Santosh Kesari1,2
1Translational Neuro-Oncology Laboratories, Moores Cancer Center, University of California San Diego, La Jolla, CA
2Division of Neuro-Oncology, Department of Neurosciences, University of California, San Diego, La Jolla, CA
3Stanford University, Palo Alto, CA
*These authors have contributed equally to this work
Santosh Kesari, e-mail: firstname.lastname@example.org
Keywords: mitochondrial p32, c-Myc, glutamine addiction, brain cancer
Received: October 21, 2014 Accepted: November 08, 2014 Published: December 22, 2014
Metabolic reprogramming is a key feature of tumorigenesis that is controlled by oncogenes. Enhanced utilization of glucose and glutamine are the best-established hallmarks of tumor metabolism. The oncogene c-Myc is one of the major players responsible for this metabolic alteration. However, the molecular mechanisms involved in Myc-induced metabolic reprogramming are not well defined. Here we identify p32, a mitochondrial protein known to play a role in the expression of mitochondrial respiratory chain complexes, as a critical player in Myc-induced glutamine addiction. We show that p32 is a direct transcriptional target of Myc and that high level of Myc in malignant brain cancers correlates with high expression of p32. Attenuation of p32 expression reduced growth rate of glioma cells expressing Myc and impaired tumor formation in vivo. Loss of p32 in glutamine addicted glioma cells induced resistance to glutamine deprivation and imparted sensitivity to glucose withdrawal. Finally, we provide evidence that p32 expression contributes to Myc-induced glutamine addiction of cancer cells. Our findings suggest that Myc promotes the expression of p32, which is required to maintain sufficient respiratory capacity to sustain glutamine metabolism in Myc transformed cells.
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