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Rejuvenation Res. 2019 Apr;22(2):138-145. doi: 10.1089/rej.2018.2089. Epub 2018 Sep 4.

STAT3/c-Myc Axis-Mediated Metabolism Alternations of Inflammation-Related Glycolysis Involve with Colorectal Carcinogenesis.

Author information

1
1 Department of Basic Medicine, Shaanxi University of Chinese Medicine, Xian yang, People's Republic of China.
2
2 Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xian yang, People's Republic of China.
3
3 School of Acupuncture and Massage, and Shaanxi University of Chinese Medicine, Xian yang, People's Republic of China.
4
4 Shaanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, Shaanxi University of Chinese Medicine, Xian yang, People's Republic of China.

Abstract

Chronic inflammation is a major driving factor for the development of colitis-associated cancer (CAC). It is extensively acknowledged that patients who have long-standing inflammation bowel disease are at high risk for developing CAC. However, the metabolic alteration by which chronic intestinal inflammation promotes colorectal cancer is unclear. In the present study, we constructed dextran sulfate sodium (DSS)-induced colitis mouse model to uncover possible alterations in the metabolism indexes. Interestingly, after DSS diet administration, the expression of metabolism indexes and c-Myc increased. Moreover, in vitro, we treated cells with IL-6 to simulate inflammatory microenvironment and found that glucose uptake, lactate production, and lactate dehydrogenase activity increased dramatically, mirroring what were observed in vivo. In addition, the associative inhibition of STAT3 and c-Myc could significantly block the expression of metabolic enzymes. With the inhibition of STAT3/c-Myc signaling, meanwhile, the upregulation of both cell glucose uptake and lactate production by IL-6 pretreatment was reduced simultaneously. Thus, our study indicates that inflammation could induce metabolic disorder by promoting STAT3 signaling and c-Myc activity. Collectively, we find that metabolic disruptions triggered by inflammatory signaling are associated with tumorigenesis via the STAT3/c-Myc axis.

KEYWORDS:

; colitis-associated cancer; inflammation; metabolism disorders

PMID:
29932015
DOI:
10.1089/rej.2018.2089

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