Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis (Cell, 2010, 140:49-61)

報告日期: 2010/03/26
報告時間: 15:10/16:00
報告學生: 謝銘育
講評老師: 蔡曜聲
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990326-1.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,* 

 

Cell (2010) January 8,140, 49–61.

 

Speaker:謝銘育

Commentator蔡曜聲 老師

Date2010/03/26

Time : 15:10-16:00

PlaceRoom 602

 

Abstract

In addition to DNA synthesis, the rapid proliferation rate in cancer cells requires tremendous amount of lipid synthesized for the formation of plasma membrane and other lipid-containing vesicles inside the cell.  In this situation, the cancer cells will require reprogramming of the metabolic pathways, including glycolysis and lipogenesis to match this requirement.  In this study, the author used functional proteomic methods and discovered a monoacylglycerol lipase (MAGL) is highly elevated in aggressive cancer cells from many types of cancer.  The authors demonstrated that MAGL regulates a fatty acid network enriched in oncogenic signaling moleucles that promotes migration, invasion, survival, and tumor growth.  Overexpression of MAGL increased the aggressiveness of cancer cell, which could be inhibited by a MAGL inhibitor (i.e. JZL184).  In addition, via high-fat diet, exogenous fatty acid can promote the malignancy of cancer cells lacking MAGL activity in mice.  These results revealed how cancer cells pair lipogenesis with lipolytic activity to generate an array of fatty acid-derived signaling molecules required for its malignant phenotype.     

 

References:

1.  Fatty Acid Synthase Inhibition Activates AMP-Activated Protein Kinase in SKOV3 Human Ovarian Cancer Cells Cancer Res 2007; 67: (7).

2.  TheM2splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth NATURE (2008) , Vol 452, 13