Authors
Li Che, Wenna Chi, Yu Qiao, Jie Zhang, Xinhua Song, Ye Liu, Lei Li, Jiaoyuan Jia, Maria G Pilo, Jingxiao Wang, Antonio Cigliano, Zhilong Ma, Wenhua Kuang, Zefang Tang, Zemin Zhang, Guanghou Shui, Silvia Ribback, Frank Dombrowski, Matthias Evert, Rosa Maria Pascale, Carla Cossu, Giovanni Mario Pes, Timothy F Osborne, Diego F Calvisi, Xin Chen, Ligong Chen
Publication date
2020/1/12
Journal
Gut
Volume
69
Issue
1
Pages
gutjnl-2018-317581
Publisher
BMJ Publishing Group
Description
Objective
Increased de novo fatty acid (FA) synthesis and cholesterol biosynthesis have been independently described in many tumour types, including hepatocellular carcinoma (HCC).
Design
We investigated the functional contribution of fatty acid synthase (Fasn)-mediated de novo FA synthesis in a murine HCC model induced by loss of Pten and overexpression of c-Met (sgPten/c-Met) using liver-specific Fasn knockout mice. Expression arrays and lipidomic analysis were performed to characterise the global gene expression and lipid profiles, respectively, of sgPten/c-Met HCC from wild-type and Fasn knockout mice. Human HCC cell lines were used for in vitro studies.
Results
Ablation of Fasn significantly delayed sgPten/c-Met-driven hepatocarcinogenesis in mice. However, eventually, HCC emerged in Fasn knockout mice. Comparative genomic and lipidomic analyses revealed the upregulation of genes …
Total citations
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