单酰甘油脂肪酶调小节促进癌症发病的一.pptVIP

单酰甘油脂肪酶调节促进癌症发病的一个脂肪酸网络Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer PathogenesisDaniel K. Nomura, Jonathan Z. Long, Sherry Niessen, Heather S. Hoover, Shu-Wing Ng and Benjamin F. Cravatt, 来自：斯克里普斯研究所  The Scripps Research Institute  崔艳娥 20092513410 Monoacylglycerol lipase (MAGL) is elevated in aggressive human cancer cells ? Loss of MAGL lowers fatty acid levels in cancer cells and impairs pathogenicity ? MAGL controls a signaling network enriched in protumorigenic lipids ? A high-fat diet can restore the growth of tumors lacking MAGL in vivo 人类癌细胞中单酰甘油脂肪酶的含量提高 癌细胞中减少的MAGL会降低脂肪酸的量以及减少致病性 MAGL调节促进癌症发病的一个脂肪酸网络 Tumor cells display progressive changes in metabolism that correlate with malignancy, including development of a lipogenic phenotype. How stored fats are liberated and remodeled to support cancer pathogenesis, however, remains unknown. Here, we show that the enzyme monoacylglycerol lipase (MAGL) is highly expressed in aggressive human cancer cells and primary tumors, where it regulates a fatty acid network enriched in oncogenic signaling lipids that promotes migration, invasion, survival, and in vivo tumor growth. Overexpression of MAGL in nonaggressive cancer cells recapitulates this fatty acid network and increases their pathogenicityphenotypes that are reversed by an MAGL inhibitor. Impairments in MAGL-dependent tumor growth are rescued by a high-fat diet, indicating that exogenous sources of fatty acids can contribute to malignancy in cancers lacking MAGL activity. Together, these findings reveal how cancer cells can co-opt a lipolytic enzyme to translate their lipogenic state into an array of protumorigenic signals 肿瘤细胞展示了在新陈代谢中的与恶性肿瘤相关的进展，包括脂肪性表型，储存的脂肪细胞摆脱束缚以及被改造后促进癌症的发病机理，然而，仍未知。这里，单酰甘油脂肪酶在人癌症细胞中和初级的肿瘤细胞中是高度表达的，调节促进癌症发病的一个脂肪酸网络，促进移动，入侵，存活，以及在活的生物体内增长。在无攻击性的癌细胞中超表达的单酰甘油脂肪酶概括了这个脂肪酸网路增加了他们的致病性表型的转变，致病性表型本是被单酰甘油脂肪酶的抑制剂抑制的，高脂肪的饮食缓解了单酰甘油脂肪酶在依赖