NCOA5 haploinsufficiency results in glucose intolerance and subsequent hepatocellular carcinoma

Cancer Cell
Shenglan GaoHua Xiao

Abstract

Type 2 diabetes (T2D) and male gender are associated with hepatocellular carcinoma (HCC) development. We demonstrate that heterozygous deletion of the Ncoa5 gene causes spontaneous development of HCC exclusively in male mice. Tumor development is preceded by increased interleukin-6 (IL-6) expression, early-onset glucose intolerance, and progressive steatosis and dysplasia in livers. Blockading IL-6 overexpression averts glucose intolerance and partially deters HCC development. Moreover, reduced NCOA5 expression is associated with a fraction of human HCCs and HCCs with comorbid T2D. These findings suggest that NCOA5 is a haploinsufficient tumor suppressor and that NCOA5 deficiency increases susceptibility to both glucose intolerance and HCC, partially by increasing IL-6 expression. Thus, our findings open additional avenues for developing therapeutic approaches to combat these diseases.

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Citations

Sep 12, 2014·Diabetologia·Yi HuangYuli Huang
Feb 13, 2016·Journal of Hepatology·Dirk Schmidt-Arras, Stefan Rose-John
Jan 15, 2014·Cell Metabolism·Debanjan DharMichael Karin
Oct 9, 2014·Endocrine·Martin BuysschaertJaqueline Lonier
Apr 6, 2017·BMC Complementary and Alternative Medicine·Lili TianGuofu Zhu
May 31, 2019·Annals of the Rheumatic Diseases·Hilal Ince-AskanRadboud J E M Dolhain
Jan 4, 2017·Endocrine·Lorenzo ScappaticcioKatherine Esposito
Jul 16, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Wanying LiJian Sun

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