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

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. +7 more·2015·Proceedings of the National Academy of Sciences

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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Crossref · 10.1073/pnas.1507228112

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  • Specific metabolic importance of glutamine in tumorigenesis and tumor growth has been reported.

    “Nevertheless, the specific metabolic importance of glutamine in tumorigenesis and tumor growth has also been reported194–196”

    From Glutamine reliance in cell metabolism (2020) · cites this paper as [196]

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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)
Venue
Proceedings of the National Academy of Sciences
Published
2015-05-11
Volume
112
Issue
21
Pages
6539-6544
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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 › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › 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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