title: ALOX15 as a suppressor of inflammation and cancer: Lost in the link.
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.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Rui
authors.initials: R
authors.lastname: Tian
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jaoude
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Fei
authors.initials: F
authors.lastname: Mao
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Colby
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States. Electronic address: ishureiqi@mdanderson.org.
authors.forename: Imad
authors.initials: I
authors.lastname: Shureiqi
mesh_terms: D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D063646:Carcinogenesis; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D005231:Fatty Acids, Unsaturated; D001093:Arachidonate 15-Lipoxygenase
keywords: ALOX15; Colitis-associated colorectal cancer; Colon cancer