title: The Hippo signal transduction pathway in soft tissue sarcomas.
abstract: Sarcomas are rare cancers (≈1% of all solid tumours) usually of mesenchymal origin. Here, we review evidence implicating the Hippo pathway in soft tissue sarcomas. Several transgenic mouse models of Hippo pathway members (Nf2, Mob1, LATS1 and YAP1 mutants) develop various types of sarcoma. Despite that, Hippo member genes are rarely point mutated in human sarcomas. Instead, WWTR1-CAMTA1 and YAP1-TFE3 fusion genes are found in almost all cases of epithelioid haemangioendothelioma. Also copy number gains of YAP1 and other Hippo members occur at low frequencies but the most likely cause of perturbed Hippo signalling in sarcoma is the cross-talk with commonly mutated cancer genes such as KRAS, PIK3CA, CTNNB1 or FBXW7. Current Hippo pathway-targeting drugs include compounds that target the interaction between YAP and TEAD G protein-coupled receptors (GPCR) and the mevalonate pathway (e.g. statins). Given that many Hippo pathway-modulating drugs are already used in patients, this could lead to early clinical trials testing their efficacy in different types of sarcoma.
authors.affiliation: School of Medical Sciences, University of Aberdeen, AB25 2ZD Scotland, UK.
authors.forename: Abdalla D
authors.initials: AD
authors.lastname: Mohamed
authors.affiliation: Stem Cell Program, Children's Hospital, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Annie M
authors.initials: AM
authors.lastname: Tremblay
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen, AB25 2ZD Scotland, UK.
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Murray
authors.affiliation: School of Medical Sciences, University of Aberdeen, AB25 2ZD Scotland, UK. Electronic address: h.wackerhage@abdn.ac.uk.
authors.forename: Henning
authors.initials: H
authors.lastname: Wackerhage
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000090683:Hippo Signaling Pathway; D006801:Humans; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D017346:Protein Serine-Threonine Kinases
keywords: Fusion genes; Hippo pathway; Rhabdomyosarcoma; Sarcoma; TAZ; YAP