Abstract
Mounting evidence supports a mechanistic link between inflammation and cancer, especially colon cancer. ALOX15 (15-lipoxygenase-1) plays an important role in the formation of key lipid mediators (e.g., lipoxins and resolvins) to terminate inflammation. ALOX15 expression is downregulated in colorectal cancer (CRC). Intestinally-targeted transgenic expression of ALOX15 in mice inhibited dextran sodium sulfate-induced colitis from promoting azoxymethane- induced colorectal tumorigenesis, demonstrating that ALOX15 can suppress inflammation-driven promotion of carcinogen-induced colorectal tumorigenesis and therefore ALOX15 downregulation during tumorigenesis is likely to enhance the link between colitis and colorectal tumorigenesis. ALOX15 suppressed the TNF-α, IL-1β/NF-κB, and IL-6/STAT3 signaling pathways, which play major roles in promotion of colorectal cancer by chronic inflammation. Defining ALOX15's regulatory role in colitis-associated colorectal cancer could identify important molecular regulatory events that could be targeted to suppress promotion of tumorigenesis by chronic inflammation.
Original language | English (US) |
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Pages (from-to) | 77-83 |
Number of pages | 7 |
Journal | Prostaglandins and Other Lipid Mediators |
Volume | 132 |
DOIs | |
State | Published - Sep 2017 |
Keywords
- ALOX15
- Colitis-associated colorectal cancer
- Colon cancer
ASJC Scopus subject areas
- Biochemistry
- Physiology
- Pharmacology
- Cell Biology
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