The Hippo signaling pathway in liver regeneration and tumorigenesis
Open Access
- 4 December 2014
- journal article
- review article
- Published by China Science Publishing & Media Ltd. in Acta Biochimica et Biophysica Sinica
- Vol. 47 (1), 46-52
- https://doi.org/10.1093/abbs/gmu106
Abstract
The Hippo signaling pathway is an evolutionarily conserved signaling module that plays critical roles in liver size control and tumorigenesis. The Hippo pathway consists of a core kinase cascade in which the mammalian Ste20-like kinases (Mst1/2, orthologs of Drosophila Hippo) and their cofactor Salvador (Sav1) form a complex to phosphorylate and activate the large tumor suppressor (Lats1/2). Lats1/2 kinases in turn phosphorylate and inhibit the transcription co-activators, the Yes-associated protein (YAP) and the transcriptional co-activator with PDZ-binding motif (TAZ), two major downstream effectors of the Hippo pathway. Losses of the Hippo pathway components induce aberrant hepatomegaly and tumorigenesis, in which YAP coordinates regulation of cell proliferation and apoptosis and plays an essential role. This review summarizes the current findings of the regulation of Hippo signaling in liver regeneration and tumorigenesis, focusing on how the loss of tumor suppressor components of the Hippo pathway results in liver cancers and discussing the molecular mechanisms that regulate the expression and activation of its downstream effector YAP in liver tumorigenesis.Keywords
This publication has 55 references indexed in Scilit:
- Human hepatic stem cell and maturational liver lineage biologyHepatology, 2011
- The Merlin/NF2 Tumor Suppressor Functions through the YAP Oncoprotein to Regulate Tissue Homeostasis in MammalsDevelopmental Cell, 2010
- Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppressionProceedings of the National Academy of Sciences of the United States of America, 2010
- Mst1 and Mst2 Maintain Hepatocyte Quiescence and Suppress Hepatocellular Carcinoma Development through Inactivation of the Yap1 OncogeneCancer Cell, 2009
- Yes‐associated protein is an independent prognostic marker in hepatocellular carcinomaCancer, 2009
- Stem cells, cell transplantation and liver repopulationBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2008
- Elucidation of a Universal Size-Control Mechanism in Drosophila and MammalsCell, 2007
- Mob as tumor suppressor is activated by Hippo kinase for growth inhibition in DrosophilaThe EMBO Journal, 2007
- Transforming properties of YAP , a candidate oncogene on the chromosome 11q22 ampliconProceedings of the National Academy of Sciences of the United States of America, 2006
- Identification and Validation of Oncogenes in Liver Cancer Using an Integrative Oncogenomic ApproachCell, 2006