Cited by 1,002Cancer, Lipids, and MetabolismLipid metabolism and biosynthesisSphingolipid Metabolism and Signaling

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Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer Pathogenesis

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Nomura, Daniel K., Long, Jonathan Z., Niessen, Sherry, Hoover, Heather S., Ng, Shu-Wing, Cravatt, Benjamin F.·2010·Cell

DOI 10.1016/j.cell.2009.11.027PMC PMC2885975

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Abstract

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:

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Authors: Nomura, D. K., Long, J. Z., Niessen, S., Hoover, H. S., Ng, S.-W., & Cravatt, B. F.
Affiliations: Scripps Research Institute (US)
Brigham and Women's Hospital (US)
Corresponding author: Cravatt, Benjamin F.
ORCID: Nomura, Daniel K.
Long, Jonathan Z.
Hoover, Heather S.
Ng, Shu-Wing
Cravatt, Benjamin F.
Venue: Cell
Publisher: Elsevier BV
Published: 2010-01
Volume: 140
Issue: 1
Pages: 49-61
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2009.11.027
PMC: PMC2885975
OpenAlex: W2127624416
Cited by: 1,002
References: 69
Citations by year: 2026: 40 · 2025: 41 · 2024: 55 · 2023: 46 · 2022: 59 · 2021: 78 · 2020: 69 · 2019: 67 · 2018: 69 · 2017: 60 · 2016: 75 · 2015: 72 · 2014: 70 · 2013: 61 · 2012: 47
FWCI: 15.66
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1293 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Cancer Institute (R01CA132630, CA-087660, R37CA087660, R01CA087660, CA132630)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords: monoacylglycerol lipase, fatty acid metabolism, lipolysis, tumor cell migration and invasion, tumor growth, MAGL inhibitors, high-fat diet, cancer metabolism
MeSH terms: Animals, Cell Line, Fatty Acids, Female, Humans, Monoacylglycerol Lipases, Neoplasm Transplantation, Ovarian Neoplasms, Transplantation, Heterologous, Tumor Cells, Cultured, Monoglycerides, Mice

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Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer Pathogenesis

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