Journal
JOURNAL OF DIABETES AND ITS COMPLICATIONS
Volume 31, Issue 7, Pages 1228-1236Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jdiacomp.2017.04.012
Keywords
PRKA; Biomarker; Carcinoma; Colon; Energy balance; Molecular pathologic epidemiology
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Funding
- U.S.A. National Institutes of Health (NIH) [K07 CA190673, R01 CA151993, R35CA197735]
- National Natural Science Foundation of China [81473472, 81200612]
- Tianjin Municipal Natural Science Foundation of China [13JCZDJC30500]
- Tianjin City High School Science &Technology Fund Planning Project [20102217]
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The recently rapid increase of obesity and type 2 diabetes mellitus has caused great burden to our society. A positive association between type 2 diabetes and risk of colorectal cancer has been reported by increasing epidemiological studies. The molecular mechanism of this connection remains elusive. However, type 2 diabetes may result in abnormal carbohydrate and lipid metabolism, high levels of circulating insulin, insulin growth factor-1, and adipocytolcines, as well as chronic inflammation. All these factors could lead to the alteration of energy sensing pathways such as the AMP activated kinase (PRKA), mechanistic (mammalian) target of rapamycin (mTOR), SIRT1, and autophagy signaling pathways. The resulted impaired SIRT1 and autophagy signaling pathway could increase the risk of gene mutation and cancer genesis by decreasing genetic stability and DNA mismatch repair. The dysregulated mTOR and PRKA pathway could remodel cell metabolism during the growth and metastasis of cancer in order for the cancer cell to survive the unfavorable microenvironment such as hypoxia and low blood supply. Moreover, these pathways may be coupling metabolic and epigenetic alterations that are central to oncogenic transformation. Further researches including molecular pathologic epidemiologic studies are warranted to better address the precise links between these two important diseases. (C) 2017 Elsevier Inc. All rights reserved.
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