Functional Lipidomics: Palmitic Acid Impairs Hepatocellular Carcinoma Development by Modulating Membrane Fluidity and Glucose Metabolism
Functional Lipidomics: Palmitic Acid Impairs Hepatocellular Carcinoma Development by Modulating Membrane Fluidity and Glucose Metabolism
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DOI：
10.1002/hep.29033
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发表时间：
2017-08-01
期刊：
影响因子：
13.5
通讯作者：
Shen, Huali
中科院分区：
文献类型：
--
作者：
Lin, Ling;Ding, Ying;Shen, Huali
脂质是生物体的基本细胞成分和能量来源，脂质组成的改变越来越被认为是癌症的标志。我们在一系列肝细胞癌（HCC）细胞中进行了脂质组学分析，并鉴定了来自三种主要脂质类别的1,700多种完整脂质。比较脂质组学筛选显示，93显著改变的脂质和减少的棕榈酸酰基（C16：0）含有甘油磷脂与肝癌细胞的转移能力呈正相关。此外，体外和体内实验均表明，C16：0孵育可特异性降低小鼠异种移植模型中的恶性细胞增殖、损害细胞侵袭力并抑制肿瘤生长。生化实验表明，C16：0处理降低细胞膜流动性和限制葡萄糖代谢。磷酸蛋白质组学方法进一步揭示了这样的C16：0孵育减弱了哺乳动物雷帕霉素靶蛋白（mTOR）和信号转导和转录激活因子3（STAT 3）途径蛋白的磷酸化水平。对443个脂质分子的多反应监测分析显示，在一组临床HCC标本中，癌组织与邻近非肿瘤组织相比，在总共10个改变的脂质中，8个含C16：0的脂质减少（P < 0.05）。结论：这些数据共同证明了使用改变的脂质代谢作为癌细胞诊断标志物的生物医学潜力，并为通过靶向改变的C16：0代谢治疗侵袭性HCC提供了机会。
Lipids are essential cellular components and energy sources of living organisms, and altered lipid composition is increasingly recognized as a signature of cancer. We performed lipidomic analysis in a series of hepatocellular carcinoma (HCC) cells and identified over 1,700 intact lipids originating from three major lipid categories. Comparative lipidomic screening revealed that 93 significantly changed lipids and decreased palmitic acyl (C16:0)-containing glycerophospholipids were positively associated with metastatic abilities of HCC cells. Furthermore, both in vitro and in vivo experiments demonstrated that C16:0 incubation specifically reduced malignant cell proliferation, impaired cell invasiveness, and suppressed tumor growth in mouse xenograft models. Biochemical experiments demonstrated that C16:0 treatment decreased cell membrane fluidity and limited glucose metabolism. A phosphoproteomics approach further revealed such C16:0 incubation attenuated phosphorylation levels of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) pathway proteins. Multiple reaction monitoring analysis of 443 lipid molecules showed 8 reduced C16:0-containing lipids out of total 10 altered lipids when cancer tissues were compared with adjacent nontumor tissues in a cohort of clinical HCC specimens (P < 0.05). Conclusion:These data collectively demonstrate the biomedical potential of using altered lipid metabolism as a diagnostic marker for cancerous cells and open an opportunity for treating aggressive HCCs by targeting altered C16:0 metabolism.