Journal
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
Volume 47, Issue 1, Pages 46-52Publisher
OXFORD UNIV PRESS
DOI: 10.1093/abbs/gmu106
Keywords
Hippo signaling; YAP; liver regeneration; liver cancer
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Funding
- China's 1000 Young Talents Program
- Ministry of Education of China [B06016]
- Fundamental Research Funds for the Central Universities of China [20720140537]
- National Natural Science Foundation of China [81101503, 31270918, 81222030, 81372617, J1310027, 81422018, 81472229]
- Natural Science Foundation of Fujian [2013J06011]
- Program of Introducing Talents of Discipline to Universities [B12001]
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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.
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