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mTORC2 promotes tumor growth via lipid synthesis

Guri, Yakir. mTORC2 promotes tumor growth via lipid synthesis. 2016, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_12145

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Abstract

Dysregulated mammalian TOR (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, lipidomic and metabolomic analyses revealed that hepatic mTORC2 promotes de novo fatty acid and lipid synthesis, and thereby tumorigenesis. In particular, mTORC2 stimulated sphingolipid (glucoceramide) and glycerophospholipid (cardiolipin) synthesis. Inhibition of fatty acid or sphingolipid synthesis prevented tumor development. Increased levels of cardiolipin were associated with tubular mitochondria and enhanced oxidative phosphorylation. Thus, mTORC2 promotes cancer via formation of lipids essential for growth and energy production. Collectively, these findings illustrate a role for mTORC2 in lipid-mediated oncogenesis that could be exploited for targeted cancer therapies.
Advisors:Hall, Michael N. and Heim, Markus H.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N. and Heim, Markus H.
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:12145
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (136, 10 Seiten)
Language:English
Identification Number:
Last Modified:22 Jan 2018 15:52
Deposited On:17 May 2017 13:58

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