(肿瘤生物学)cellMonoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer Pathogenesis.pdf

Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer Pathogenesis Daniel K. Nomura,1 Jonathan Z. Long,1 Sherry Niessen,2 Heather S. Hoover,2 Shu-Wing Ng,3 and Benjamin F. Cravatt1,* 1The Skaggs Institute for Chemical Biology and Department of Chemical Physiology 2The Center for Physiological Proteomics The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA 3Laboratory of Gynecologic Oncology, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA *Correspondence: cravatt@scripps.edu DOI 10.1016/j.cell.2009.11.027 SUMMARY in disease progression and malignancy. Answers to these ques- tions are important for identifying metabolic pathways that are Tumor cells display progressive changes in metabo- vital to the pathogenesis of cancer. lism that correlate with malignancy, including devel- Among dysregulated metabolic pathways, heightened de opment of a lipogenic phenotype. How stored fats novo lipid biosynthesis, or the development of a ‘‘lipogenic’’ are liberated and remodeled to support cancer phenotype (Menendez and Lupu, 2007), has been posited to pathogenesis, however, remains unknown. Here, play a major role in cancer. For instance, elevated levels of fatty acid synthase (FAS), the enzyme responsible for fatty acid we show that the enzyme monoacylglycerol lipase biosynthesis from acetate and malonyl CoA, are correlated (MAGL) is highly expressed in aggressive human