Eicosanoid signaling in carcinogenesis of colorectal cancer

Cancer Metastasis Rev. 2018 Sep;37(2-3):257-267. doi: 10.1007/s10555-018-9739-8.

Abstract

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in the USA. It is of practical importance to identify novel therapeutic targets of CRC to develop new anti-cancer drugs and to discover novel biomarkers of CRC to develop new detection methods. Eicosanoids, which are metabolites of polyunsaturated fatty acids produced by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes, are important lipid-signaling molecules involved in the regulation of inflammation and tumorigenesis. Substantial studies have shown that the profiles of eicosanoids are deregulated in CRC, and the enzymes, metabolites, and receptors in the eicosanoid signaling cascade play critical roles in regulating colonic inflammation and colon tumorigenesis. In this review, we discuss the roles of the COX, LOX, and CYP pathways in the carcinogenesis of CRC.

Keywords: Colonic inflammation; Colorectal cancer; Cyclooxygenase; Cytochrome P450; Eicosanoids; Lipoxygenase; Obesity; Soluble epoxide hydrolase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Colitis / complications
  • Colitis / metabolism
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Eicosanoids / metabolism*
  • Epoxide Hydrolases / genetics
  • Epoxide Hydrolases / metabolism
  • Humans
  • Lipid Metabolism
  • Lipoxygenase / genetics
  • Lipoxygenase / metabolism
  • Obesity / complications
  • Obesity / metabolism
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Signal Transduction*

Substances

  • Eicosanoids
  • Cytochrome P-450 Enzyme System
  • Lipoxygenase
  • Prostaglandin-Endoperoxide Synthases
  • Epoxide Hydrolases