State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, the Institute for Advanced Studies, Wuhan University, Wuhan, China.
Hepatology. 2017 Jun;65(6):1936-1947. doi: 10.1002/hep.29018. Epub 2017 Apr 18.
Obesity is a critical risk factor for hepatocellular carcinoma (HCC). However, it remains unknown whether inhibition of de novo lipid biosynthesis can suppress HCC. In this study, we blocked the sterol regulatory element-binding protein (SREBP) pathway, one of the key determinants of lipid homeostasis, by ablating 78-kDa cell-surface glycoprotein or SREBP cleavage-activating protein in hepatocytes, as well as by administering a chemical compound called betulin. We found that either genetically or pharmacologically inhibiting the SREBP pathway dramatically reduced diethylnitrosamine-induced HCC progression by down-regulating tumor-promoting cytokines, including interleukin (IL)-6, tumor necrosis factor alpha, and IL-1β.
Inhibition of de novo lipid biosynthesis by suppressing the SREBP pathway prevents HCC. This study identifies a previously underappreciated role of the SREBP pathway in HCC and suggests a novel metabolic strategy to control liver cancer. (Hepatology 2017;65:1936-1947).
肥胖是肝细胞癌（HCC）的一个关键危险因素。然而，目前尚不清楚是否可以抑制从头合成脂质来抑制 HCC。在这项研究中，我们通过在肝细胞中敲除 78kDa 细胞表面糖蛋白或 SREBP 裂解激活蛋白，以及使用一种名为 betulin 的化学化合物，阻断了固醇调节元件结合蛋白（SREBP）途径，该途径是脂质动态平衡的关键决定因素之一。我们发现，通过下调促肿瘤细胞因子，包括白细胞介素（IL）-6、肿瘤坏死因子-α和 IL-1β，无论是遗传还是药理学抑制 SREBP 途径，都能显著降低二乙基亚硝胺诱导的 HCC 进展。
通过抑制 SREBP 途径抑制从头合成脂质可预防 HCC。本研究确定了 SREBP 途径在 HCC 中的一个以前被低估的作用，并提出了一种控制肝癌的新的代谢策略。（《肝脏病学》2017；65：1936-1947）。
