title: The Hippo signaling pathway in liver regeneration and tumorigenesis.
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.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Hong
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Yabo
authors.initials: Y
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
authors.forename: Mingting
authors.initials: M
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China chenlanfen@xmu.edu.cn dwzhou@xmu.edu.cn.
authors.forename: Dawang
authors.initials: D
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China chenlanfen@xmu.edu.cn dwzhou@xmu.edu.cn.
authors.forename: Lanfen
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D063646:Carcinogenesis; D049109:Cell Proliferation / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D000090683:Hippo Signaling Pathway; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology*; D008115:Liver Regeneration / Q000502:physiology*; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D000091102:YAP-Signaling Proteins
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; D017346:Protein Serine-Threonine Kinases
keywords: Hippo signaling; YAP; liver cancer; liver regeneration