The Oncoprotein Gankyrin/PSMD10 as a Target of Cancer Therapy.

The Oncoprotein Gankyrin/PSMD10 as a Target of Cancer Therapy. Adv Exp Med Biol. 2019;1164:63-71 Authors: Fujita J, Sakurai T Abstract Gankyrin (also called PSMD10, p28, or p28GANK) is a crucial oncoprotein that is upregulated in various cancers and assumed to play pivotal roles in the initiation and progression of tumors. Although the in vitro function of gankyrin is relatively well characterized, its role in vivo remains to be elucidated. We have investigated the function of gankyrin in vivo by producing mice with liver parenchymal cell-specific gankyrin ablation (Alb-Cre;gankyrinf/f) and gankyrin deletion both in liver parenchymal and in non-parenchymal cells (Mx1-Cre;gankyrinf/f). Gankyrin deficiency both in non-parenchymal cells and parenchymal cells, but not in parenchymal cells alone, reduced STAT3 activity, interleukin-6 production, and cancer stem cell marker expression, leading to attenuated tumorigenic potential in the diethylnitrosamine hepatocarcinogenesis model. Essentially similar results were obtained by analyzing mice with intestinal epithelial cell-specific gankyrin ablation (Villin-Cre;Gankyrinf/f) and gankyrin deletion both in myeloid and epithelial cells (Mx1-Cre;Gankyrinf/f) in the colitis-associated cancer model. Clinically, gankyrin expression in the tumor microenvironment was negatively correlated with progression-free survival in patients undergoing treatment with Sorafenib for hepatocellular carcinomas. ...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research