Scientific article
Open access

mTORC2 Promotes Tumorigenesis via Lipid Synthesis

Published inCancer Cell, vol. 32, no. 6, p. 807-823.e12
Publication date2017

Dysregulated mammalian target of rapamycin (mTOR) promotes cancer, but underlying mechanisms are poorly understood. We describe an mTOR-driven mouse model that displays hepatosteatosis progressing to hepatocellular carcinoma (HCC). Longitudinal proteomic, lipidomics, and metabolomic analyses revealed that hepatic mTORC2 promotes de novo fatty acid and lipid synthesis, leading to steatosis and tumor development. In particular, mTORC2 stimulated sphingolipid (glucosylceramide) and glycerophospholipid (cardiolipin) synthesis. Inhibition of fatty acid or sphingolipid synthesis prevented tumor development, indicating a causal effect in tumorigenesis. Increased levels of cardiolipin were associated with tubular mitochondria and enhanced oxidative phosphorylation. Furthermore, increased lipogenesis correlated with elevated mTORC2 activity and HCC in human patients. Thus, mTORC2 promotes cancer via formation of lipids essential for growth and energy production.

  • Cardiolipin
  • Glycosphingolipid
  • Hepatocellular carcinoma
  • Hepatosteatosis
  • Mitochondria
  • MTOR
  • NASH
  • Oxidative phosphorylation
  • Sphingolipid
Citation (ISO format)
GURI, Yakir et al. mTORC2 Promotes Tumorigenesis via Lipid Synthesis. In: Cancer Cell, 2017, vol. 32, n° 6, p. 807–823.e12. doi: 10.1016/j.ccell.2017.11.011
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Article (Published version)
ISSN of the journal1535-6108

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