The MYC Oncogene Cooperates with Sterol-Regulated Element-Binding Protein to Regulate Lipogenesis Essential for Neoplastic Growth

Arvin M. Gouw, Katherine Margulis, Natalie S. Liu, Sudha J. Raman, Anthony Mancuso, Georgia G. Toal, Ling Tong, Adriane Mosley, Annie L. Hsieh, Delaney K. Sullivan, Zachary E. Stine, Brian J. Altman, Almut Schulze, Chi V. Dang*, Richard N. Zare, Dean W. Felsher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


Lipid metabolism is frequently perturbed in cancers, but the underlying mechanism is unclear. We present comprehensive evidence that oncogene MYC, in collaboration with transcription factor sterol-regulated element-binding protein (SREBP1), regulates lipogenesis to promote tumorigenesis. We used human and mouse tumor-derived cell lines, tumor xenografts, and four conditional transgenic mouse models of MYC-induced tumors to show that MYC regulates lipogenesis genes, enzymes, and metabolites. We found that MYC induces SREBP1, and they collaborate to activate fatty acid (FA) synthesis and drive FA chain elongation from glucose and glutamine. Further, by employing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), we observed in vivo lipidomic changes upon MYC induction across different cancers, for example, a global increase in glycerophosphoglycerols. After inhibition of FA synthesis, tumorigenesis was blocked, and tumors regressed in both xenograft and primary transgenic mouse models, revealing the vulnerability of MYC-induced tumors to the inhibition of lipogenesis. Gouw and Margulis et al. present comprehensive evidence that the oncogene MYC collaborates with the transcription factor SREBP1 in controlling lipogenesis to promote tumorigenesis. Utilizing multiple MYC-induced tumor models, they both identify key lipogenesis genes, enzymes, and metabolites affected by MYC and expose the vulnerability of MYC cancers to lipogenesis inhibition.

Original languageAmerican English
Pages (from-to)556-572.e5
JournalCell Metabolism
Issue number3
StatePublished - 3 Sep 2019
Externally publishedYes

Bibliographical note

Funding Information:
We thank current and former members of the Dang, Felsher, Schulze, and Zare laboratories for their helpful suggestions during this project. We thank Livia Eberlin, Emelyn Shroff, Michael Wolfgang, Yunqi Lu, and Anne Le for their help. A.M.G. and K.M. are grateful to the Stanford Cancer Translational Nanotechnology Training (TNT) T32 training grant funded by the National Cancer Institute ( T32 CA196585 ) and the Stanford Center of Molecular Analysis and Design , respectively. This work is supported by the National Institutes of Health under R01 CA184384 (D.W.F. and R.N.Z.), U01 CA188383 (D.W.F.), R01 CA208735 PQ7 (D.W.F.), R01 CA051497 (C.V.D.), R01 CA057341 (C.V.D.), and the German Research Foundation ( SCHU2670 ).

Publisher Copyright:
© 2019 Elsevier Inc.


  • ChIP
  • MYC
  • MYC conditional transgenic mouse models
  • RNA-seq
  • SREBP1
  • acetyl-CoA carboxylase A inhibition
  • carbon tracing
  • fatty acid synthesis
  • glycerophosphoglycerols
  • mass spectrometry imaging
  • nuclear run-on


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