title: One Hippo and many masters: differential regulation of the Hippo pathway in cancer.
abstract: The Hippo/MST2 (mammalian sterile 20-like kinase 2) pathway is a signalling cascade evolutionarily conserved in its structure. Originally described in Drosophila melanogaster as a regulator of organ size, this pathway has greater functions in mammals. Disturbance of mammalian MST2 pathway is associated with tumorigenesis by affecting apoptosis, cell cycle and polarity. In addition, this pathway has been shown to cross-talk with mitogenic pathways at multiple levels. In the present mini-review, we discuss our contribution highlighting the regulation of MST2 signalling by frequently observed oncogenic perturbations affecting mitogenic pathways. In particular, we review the role of RAS isoforms and PI3K (phosphoinositide 3-kinase)/Akt in the regulation of MST2 activity by phosphorylation. We also put the emphasis on RAF-induced control of MST2 signalling by protein-protein interactions. Finally, we recapitulate some of the direct mechanisms, such as ubiquitin-dependent degradation or gene silencing by promoter hypermethylation, involved in MST2 pathway component down-regulation in cancers.
authors.affiliation: *Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Romano
authors.affiliation: *Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Matallanas
authors.affiliation: †Division of Surgical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, U.S.A.
authors.forename: Dennie T
authors.initials: DT
authors.lastname: Frederick
authors.affiliation: ‡Division of Medical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, U.S.A.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.forename: Walter
authors.initials: W
authors.lastname: Kolch
mesh_terms: D000818:Animals; D000090683:Hippo Signaling Pathway; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction / Q000187:drug effects; D018631:ras Proteins / Q000378:metabolism; D000099317:Hippo Kinases
chemical_list: D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; D018631:ras Proteins; C097835:STK3 protein, human; D000099317:Hippo Kinases