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Published in:

01-12-2011

EET signaling in cancer

Authors: Dipak Panigrahy, Emily R. Greene, Ambra Pozzi, Dao Wen Wang, Darryl C. Zeldin

Published in: Cancer and Metastasis Reviews | Issue 3-4/2011

Abstract

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.

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Title: EET signaling in cancer
Authors: Dipak Panigrahy
Emily R. Greene
Ambra Pozzi
Dao Wen Wang
Darryl C. Zeldin
Publication date: 01-12-2011
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 3-4/2011
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-011-9315-y

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