Document Detail


EET signaling in cancer.
MedLine Citation:
PMID:  22009066     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inflammation and angiogenesis in the tumor microenvironment are increasingly implicated in tumorigenesis. Endogenously produced lipid autacoids, locally acting small-molecule mediators, play a central role in inflammation and tissue homeostasis. These lipid mediators, collectively referred to as eicosanoids, have recently been implicated in cancer. Although eicosanoids, including prostaglandins and leukotrienes, are best known as products of arachidonic acid metabolism by cyclooxygenases and lipoxygenases, arachidonic acid is also a substrate for another enzymatic pathway, the cytochrome P450 (CYP) system. This eicosanoid pathway consists of two main branches: ω-hydroxylases which converts arachidonic acid to hydroxyeicosatetraenoic acids (HETEs) and epoxygenases which converts it to four regioisomeric epoxyeicosatrienoic acids (EETs; 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET). EETs regulate inflammation and vascular tone. The bioactive EETs are produced predominantly in the endothelium and are mainly metabolized by soluble epoxide hydrolase to less active dihydroxyeicosatrienoic acids. EET signaling was originally studied in conjunction with inflammatory and cardiovascular disease. Arachidonic acid and its metabolites have recently stimulated great interest in cancer biology. To date, most research on eicosanoids in cancer has focused on the COX and LOX pathways. In contrast, the role of cytochrome P450-derived eicosanoids, such as EETs and HETEs, in cancer has received little attention. While CYP epoxygenases are expressed in human cancers and promote human cancer metastasis, the role of EETs (the direct products of CYP epoxygenases) in cancer remains poorly characterized. In this review, the emerging role of EET signaling in angiogenesis, inflammation, and cancer is discussed.
Authors:
Dipak Panigrahy; Emily R Greene; Ambra Pozzi; Dao Wen Wang; Darryl C Zeldin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Cancer metastasis reviews     Volume:  30     ISSN:  1573-7233     ISO Abbreviation:  Cancer Metastasis Rev.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-14     Completed Date:  2012-04-02     Revised Date:  2013-12-11    
Medline Journal Info:
Nlm Unique ID:  8605731     Medline TA:  Cancer Metastasis Rev     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  525-40     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
8,11,14-Eicosatrienoic Acid / analogs & derivatives*,  metabolism*
Animals
Cell Transformation, Neoplastic
Cytochrome P-450 Enzyme System / genetics,  metabolism
Humans
Inflammation / metabolism
Neoplasms / blood supply,  enzymology,  metabolism*
Neovascularization, Pathologic / metabolism
Signal Transduction*
Tumor Microenvironment
Grant Support
ID/Acronym/Agency:
2P01DK38226/DK/NIDDK NIH HHS; P01 DK038226/DK/NIDDK NIH HHS; R01 CA148633/CA/NCI NIH HHS; R01CA148633-O1A1/CA/NCI NIH HHS; Z01 ES025034/ES/NIEHS NIH HHS; Z01 ES025034-14/ES/NIEHS NIH HHS; Z01 ES050167/ES/NIEHS NIH HHS; Z01 ES050167-10/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
7324-41-6/8,11,14-Eicosatrienoic Acid; 9035-51-2/Cytochrome P-450 Enzyme System
Comments/Corrections

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