Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer Pathogenesis

نویسندگان

  • Daniel K. Nomura
  • Jonathan Z. Long
  • Sherry Niessen
  • Heather S. Hoover
  • Shu-Wing Ng
  • Benjamin F. Cravatt
چکیده

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 pathogenicity-phenotypes 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. PAPERFLICK:

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Monoacylglycerol lipase promotes metastases in nasopharyngeal carcinoma.

Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes monoacylglycerides into free fatty acids and glycerol. It has recently been found to be involved in cancer progression through the free fatty acid or endocannabinoid network after studies on its function in the endocannabinoid system. Here, we determined a role for MAGL in nasopharyngeal carcinoma (NPC), which is known for its...

متن کامل

Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer.

Cancer cells couple heightened lipogenesis with lipolysis to produce fatty acid networks that support malignancy. Monoacylglycerol lipase (MAGL) plays a principal role in this process by converting monoglycerides, including the endocannabinoid 2-arachidonoylglycerol (2-AG), to free fatty acids. Here, we show that MAGL is elevated in androgen-independent versus androgen-dependent human prostate ...

متن کامل

Hydrolysis of rat chylomicron acylglycerols: a kinetic model.

A quantitative model describing the kinetics of hydrolysis of rat chylomicron acylglycerols by bovine milk lipoprotein lipase has been developed using data from studies on rat lymph chylomicrons containing doubly labeled acylglycerols. The detailed analysis indicates that, in addition to hydrolysis from tri- to di-, di- to mono-, and monoacylglycerol to glycerol, and apparently direct hydrolysi...

متن کامل

Therapeutic potential of monoacylglycerol lipase inhibitors.

Marijuana and aspirin have been used for millennia to treat a wide range of maladies including pain and inflammation. Both cannabinoids, like marijuana, that exert anti-inflammatory action through stimulating cannabinoid receptors, and cyclooxygenase (COX) inhibitors, like aspirin, that suppress pro-inflammatory eicosanoid production have shown beneficial outcomes in mouse models of neurodegene...

متن کامل

Hydrolysis of monoacylglycerol in lipoprotein remnants catalyzed by the liver plasma membrane monoacylglycerol acyltransferase.

Experiments were carried out to study the role played by the extrahepatic and hepatic lipolytic enzymes in lipoprotein catabolism. Chylomicra and very low density lipoproteins containing [I-“Hlglyceryl triacylglycerols radiolabeled in uiuo were incubated with purified milk lipoprotein lipase to produce lipoprotein remnants rich in monoacylglycerol. The primary products of the milk lipoprotein l...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Cell

دوره 140  شماره 

صفحات  -

تاریخ انتشار 2010