Cited by 256Cancer, Hypoxia, and MetabolismRenal cell carcinoma treatmentFerroptosis and cancer prognosis

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MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism

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Shroff, Emelyn H., Eberlin, Livia S., Dang, Vanessa M., Gouw, Arvin M., Gabay, Meital, Adam, Stacey J., Bellovin, David I., Tran, Phuoc T., Philbrick, William M., Garcia-Ocana, Adolfo, Casey, Stephanie C., Li, Yulin, Dang, Chi V., Zare, Richard N., Felsher, Dean W.·2015·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1507228112PMC PMC4450371

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Abstract

Significance: The absence of appropriate transgenic animal models of renal cell carcinomas (RCCs) has made it difficult to identify and test new therapies for this disease. We developed a new transgenic mouse model of a highly aggressive form of RCC in which tumor growth and regression is conditionally regulated by the MYC oncogene. Using desorption electrospray ionization–mass-spectrometric imaging, we found that certain glycerophosphoglycerols and metabolites of the glutaminolytic pathway were higher in abundance in RCC than in normal kidney tissue. Up-regulation of glutaminolytic genes and proteins was identified by genetic analysis and immunohistochemistry, therefore suggesting that RCC tumors are glutamine addicted. Pharmacological inhibition of glutaminase slowed tumor progression in vivo, which may represent a novel therapeutic route for RCC.

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Authors: Shroff, E. H., Eberlin, L. S., Dang, V. M., Gouw, A. M., Gabay, M., Adam, S. J., Bellovin, D. I., Tran, P. T., Philbrick, W. M., Garcia-Ocana, A., Casey, S. C., Li, Y., Dang, C. V., Zare, R. N., & Felsher, D. W.
Affiliations: Division of Medical Oncology, Departments of Medicine and Pathology, and
Department of Chemistry, Stanford University School of Medicine, Stanford, CA 94305;
Abramson Cancer Center (US)
Johns Hopkins University (US)
Yale University (US)
Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029
Stanford Medicine (US)
ORCID: Shroff, Emelyn H.
Dang, Vanessa M.
Gouw, Arvin M.
Adam, Stacey J.
Bellovin, David I.
Tran, Phuoc T.
Philbrick, William M.
Casey, Stephanie C.
Dang, Chi V.
Zare, Richard N.
Felsher, Dean W.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2015-05-11
Volume: 112
Issue: 21
Pages: 6539-6544
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1507228112
PMC: PMC4450371
OpenAlex: W1772301402
Cited by: 255
References: 64
Citations by year: 2026: 11 · 2025: 22 · 2024: 23 · 2023: 22 · 2022: 34 · 2021: 24 · 2020: 29 · 2019: 18 · 2018: 22 · 2017: 26 · 2016: 20 · 2015: 4
FWCI: 7.93
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.pnas.org/site/misc/userlicense.xhtml (vor, 184 d)
Locations: Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: HHS | National Institutes of Health (CA 089305, 105102, 170378)
HHS | NIH | National Cancer Institute (CA 114747, CA 112973, U01 CA188383, CA034233, CA 184384)
Leukemia and Lymphoma Society (R6223-07)
American Lung Association (RT-169741-N)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
Keywords: MYC oncogene, renal cell carcinoma, glutamine metabolism, glutaminolysis, oncogenic Ras, tumor progression, cancer metabolism, desorption electrospray ionization mass spectrometry imaging
MeSH terms: Animals, Carcinoma, Renal Cell, Disease Models, Animal, Enzyme Inhibitors, Glutaminase, Glutamine, Humans, Kidney Neoplasms, Mice, Transgenic, Genes, ras, RNA, Messenger, RNA, Neoplasm, Sulfides, Thiadiazoles, Up-Regulation, Genes, myc, Mice, SCID, Disease Progression, Spectrometry, Mass, Electrospray Ionization, Cell Line, Tumor, Lipid Metabolism, Mice

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MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism

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