Glucagon phosphorylates serine 552 of β-catenin leading to increased expression of cyclin D1 and c-Myc in the isolated rat liver

被引:13
作者
Chowdhury, Md. Kamrul H. [1 ]
Montgomery, Magda K. [1 ]
Morris, Margaret J. [1 ]
Cognard, Emmanuelle [2 ]
Shepherd, Peter R. [2 ]
Smith, Greg C. [1 ]
机构
[1] UNSW Australia, Dept Pharmacol, Sydney, NSW, Australia
[2] Univ Auckland, Dept Mol Med & Pathol, Auckland 1, New Zealand
关键词
beta-Catenin; cancer; glucagon; T2D; PREEXISTING DIABETES-MELLITUS; CANCER-RISK; COLORECTAL-CANCER; HEPATOCELLULAR CARCINOMAS; INSULIN-RESISTANCE; MOLECULAR LINKS; PROSTATE-CANCER; KIDNEY CANCER; GLUCOSE; METAANALYSIS;
D O I
10.3109/13813455.2015.1048693
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In the last 20 years the prevalence of metabolic disorders, in particular type 2 diabetes (T2D), has more than doubled. Recently, a strong link between T2D and cancer, in particularly liver cancer has been reported. However, the mechanism connecting the development of type 2 diabetes and cancer remains unknown. One of the biggest drivers of liver cancer is alterations in the Wnt/beta-catenin pathway. In this study, we aimed to identify the effect of glucagon on beta-catenin in the isolated rat liver. We found glucagon, which is substantially raised in patients with T2D, rapidly phosphorylates beta-catenin on serine 552 that is associated with increased expression of genes cyclin D1 (CCND1) and c-Myc (MYC), which are known to be involved in liver cancer. This finding may explain the increased risk of liver cancer in people with T2D.
引用
收藏
页码:88 / 96
页数:9
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