Move over Warburg: Unleashed lipid metabolism drives tumorogenesis

Granted, here at the Lipid Corner we tend to have a lipocentric view of the universe.  But there does appear to be increasing recognition that altered lipid metabolism is crucial for the tumorogenic phenotype.  Examples of this include increased fatty acid synthesis (for a nice review, see Menendez, J.A. and Lupu, R. 2007. Nat. Rev. Cancer 7:763-777) and a focus on choline kinase as a pro-oncogenic enzyme (see, for example, Yalcin et al, 2010, Oncogene  29:139-49).  In a recent article Benjamin Cravatt and colleagues have raised the stakes by demonstrating that lipid metabolism triggered by elevated monoacylglycerol lipase activity is a critical component of the aggressive tumorogenic phenotype in a number of cancer types (1).  Striking a blow for biochemists everywhere, the Cravatt group made the association by using what Cravatt calls "activity-based proteomics" (rather than the ubiquitous gene expression or standard proteomic screens) that scans for differences in enzymes that are serine hydrolases.  Two such enzymes were associated with the aggressive phenotype, one of which was monoacylglycerol lipase.  These workers demonstrate, using genetic and pharmacological techniques, that activity of monoacylglycerol lipase drives the tumorogenic phenotype in vitro and in vivo.  Further, they show that it is the released fatty acids that mediate this effect, not the reduced levels of monoacylglycerol.  What happens downstream from fatty acid release remains to be nailed down, but these authors suggest that the production of the lipid signaling molecules lysophosphatidic acid and/or prostaglandins may be important consequences.  The complexity of lipid metabolic pathways presents a challenge to discovering the precise elements of altered lipid metabolism that promote tumor cell growth and survival.  However it is clear that lipid biochemists are taking their rightful place alongside other molecular biologists in joining the fight against the scourge of cancer. 

1. Nomura DK, Long JZ, Niessen S, Hoover HS, Ng SW, Cravatt BF. Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer Pathogenesis. Cell 140:49-61, 2010

Reviewed by: Binks Wattenberg
Posted on: 09 February 2010