The Hippo–Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis

• DOI: 10.1073/pnas.0912203107
• Publication Date: 2010-04-20T03:40:15Z
• Authors: Kwang-Pyo Lee; Joo-Hyeon Lee; Tae-Shin Kim; Tack-Hoon Kim; Hee-Dong Park; Jin-Seok Byun; Min-Chul Kim; Won-Il Jeong; Diego F. Calvisi; Jin-Man Kim; Dae-Sik Lim
• Keywords: Hippo signaling pathway; Liver cell

Loss of Hippo signaling in Drosophila leads to tissue overgrowth as a result increased cell proliferation and decreased death. YAP (a homolog Yorkie target the pathway) was recently implicated control organ size, epithelial development, tumorigenesis mammals. However, role mammalian pathway such regulation has remained unclear. We now show that mice with liver-specific ablation WW45 Salvador adaptor for kinase) manifest liver size expansion hepatic progenitor cells (oval cells) eventually develop hepatomas. Moreover, abundance induced its localization nucleus oval cells, likely accounting their proliferative capacity, but not hepatocytes. Liver tumors developed heterozygous deletion or showed mixed pathology combining characteristics hepatocellular carcinoma cholangiocarcinoma seemed originate from cells. Together, our results suggest Hippo–Salvador restricts thereby controls prevents development cell–derived tumors.