title: The Hippo pathway and apico-basal cell polarity.
abstract: The establishment and maintenance of apico-basal cell polarity is a pre-requisite for the formation of a functioning epithelial tissue. Many lines of evidence suggest that cell polarity perturbations favour cancer formation, even though the mechanistic basis for this link remains unclear. Studies in Drosophila have uncovered complex interactions between the conserved Hpo (Hippo) tumour suppressor pathway and apico-basal polarity determinants. The Hpo pathway is a crucial growth regulatory network whose inactivation in Drosophila epithelial tissues induces massive overproliferation. Its core consists of a phosphorylation cascade (comprising the kinases Hpo and Warts) that mediates the inactivation of the pro-growth transcriptional co-activator Yki [Yorkie; YAP (Yes-associated protein) in mammals]. Several apically located proteins, such as Merlin, Expanded or Kibra, have been identified as upstream regulators of the Hpo pathway, leading to the notion that an apical multi-molecular complex modulates core kinase activity and promotes Yki/YAP inactivation. In the present review, we explore the links between apico-basal polarity and Hpo signalling. We focus on the regulation of Yki/YAP by apical proteins, but also on how the Hpo pathway might in turn influence apical domain size as part of a regulatory feedback loop.
authors.affiliation: Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Genevet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tapon
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D017124:Conserved Sequence / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases