Che, Li and Pilo, Maria G. and Cigliano, Antonio and Latte, Gavinella and Simile, Maria M. and Ribback, Silvia and Dombrowski, Frank and Evert, Matthias and Chen, Xin and Calvisi, Diego F. (2017) Oncogene dependent requirement of fatty acid synthase in hepatocellular carcinoma. CELL CYCLE, 16 (6). pp. 499-507. ISSN 1538-4101, 1551-4005
Full text not available from this repository. (Request a copy)Abstract
Hepatocellular carcinoma (HCC), the most frequent primary tumor of the liver, is an aggressive cancer type with limited treatment options. Cumulating evidence underlines a crucial role of aberrant lipid biosynthesis (a process known as de novo lipogenesis) along carcinogenesis. Previous studies showed that suppression of fatty acid synthase (FASN), the major enzyme responsible for de novo lipogenesis, is highly detrimental for the in vitro growth of HCC cell lines. To assess whether de novo lipogenesis is required for liver carcinogenesis, we have generated various mouse models of liver cancer by stably overexpressing candidate oncogenes in the mouse liver via hydrodynamic gene delivery. We found that overexpression of FASN in the mouse liver is unable to malignantly transform hepatocytes. However, genetic deletion of FASN totally suppresses hepatocarcinogenesis driven by AKT and AKT/c-Met protooncogenes in mice. On the other hand, liver tumor development is completely unaffected by FASN depletion in mice coexpressing b-catenin and c-Met. Our data indicate that tumors might be either addicted to or independent from de novo lipogenesis for their growth depending on the oncogenes involved. Additional investigation is required to unravel the molecular mechanisms whereby some oncogenes render cancer cells resistant to inhibition of de novo lipogenesis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CANCER-CELLS; THERAPEUTIC TARGET; MOUSE MODELS; LUNG-CANCER; METABOLISM; LIVER; MICE; GROWTH; ROLES; HOMEOSTASIS; beta-catenin; AKT; c-Met; de novo lipogenesis; FASN; targeted therapies |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 12:57 |
| Last Modified: | 20 Feb 2019 12:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/54 |
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