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mTORC2 Promotes Tumorigenesis via Lipid Synthesis

Guri, Yakir and Colombi, Marco and Dazert, Eva and Hindupur, Sravanth K. and Roszik, Jason and Moes, Suzette and Jenoe, Paul and Heim, Markus H. and Riezman, Isabelle and Riezman, Howard and Hall, Michael N.. (2017) mTORC2 Promotes Tumorigenesis via Lipid Synthesis. Cancer Cell, 32 (6). pp. 807-832.

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Official URL: http://edoc.unibas.ch/57710/

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Abstract

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 devel- opment. In particular, mTORC2 stimulated sphingolipid (glucosylceramide) and glycerophospholipid (cardi- olipin) 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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
ISSN:1535-6108
e-ISSN:1878-3686
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:28 Sep 2018 12:58
Deposited On:14 Dec 2017 10:51

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