Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma

The Hippo pathway is an evolutionarily conserved modulator of developmental biology with a key role in tissue and organ size regulation under homeostatic conditions. Like other signaling pathways with a significant role in embryonic development, the deregulation of Hippo signaling contributes to onc...

ver descrição completa

Detalhes bibliográficos
Autores: Salguero-Aranda, Carmen, Olmedo-Pelayo, Joaquín, Álava, Enrique de, Amaral, Ana Teresa, Díaz-Martín, J.
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2022
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/306808
Acesso em linha:http://hdl.handle.net/10261/306808
https://api.elsevier.com/content/abstract/scopus_id/85144928549
Access Level:Acceso aberto
Palavra-chave:Sarcoma
Hippo pathway
TAZ
YAP
Gene fusions
id ES_3b83fcb4f9a004b0afd33ee7dfb25e19
oai_identifier_str oai:digital.csic.es:10261/306808
network_acronym_str ES
network_name_str España
repository_id_str
spelling Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue SarcomaSalguero-Aranda, CarmenOlmedo-Pelayo, JoaquínÁlava, Enrique deAmaral, Ana TeresaDíaz-Martín, J.SarcomaHippo pathwayTAZYAPGene fusionsThe Hippo pathway is an evolutionarily conserved modulator of developmental biology with a key role in tissue and organ size regulation under homeostatic conditions. Like other signaling pathways with a significant role in embryonic development, the deregulation of Hippo signaling contributes to oncogenesis. Central to the Hippo pathway is a conserved cascade of adaptor proteins and inhibitory kinases that converge and regulate the activity of the oncoproteins YAP and TAZ, the final transducers of the pathway. Elevated levels and aberrant activation of YAP and TAZ have been described in many cancers. Though most of the studies describe their pervasive activation in epithelial neoplasms, there is increasing evidence pointing out its relevance in mesenchymal malignancies as well. Interestingly, somatic or germline mutations in genes of the Hippo pathway are scarce compared to other signaling pathways that are frequently disrupted in cancer. However, in the case of sarcomas, several examples of genetic alteration of Hippo members, including gene fusions, have been described during the last few years. Here, we review the current knowledge of Hippo pathway implication in sarcoma, describing mechanistic hints recently reported in specific histological entities and how these alterations represent an opportunity for targeted therapy in this heterogeneous group of neoplasm.E.d.Á.’s laboratory is supported by ISCIIIFEDER (PI20/00003) to E.d.Á., Consejería de Salud y Familias, Junta de Andalucía (PE-0186-2018) to E.d.Á. and (PI-0061-2020) to C.S.-A. and E.d.Á., GEIS (Beca José María Buesa) to A.T.A., GEIS-Fundación Mari Paz Jiménez Casado (Beca Trienal a la Investigación en Sarcomas) to J.D.-M., Fundación CRIS Contra el Cáncer, Asociación Pablo Ugarte, Fundación María García Estrada and CIBERONC. C.S.-A. is supported by the European Social Fund and the Junta de Andalucía (Talento Doctores 2020, DOC_01473), J.O.-P. is granted by a pre-doctoral fellowship from the VI Plan Propio from the Universidad de Sevilla; A.T.A. is supported Juan de la Cierva Incorporación fellowship (IJC-2018-036767-I), and J.D.-M. is supported by CIBERONC (CB16/12/00361).Peer reviewedMultidisciplinary Digital Publishing InstituteInstituto de Salud Carlos IIIEuropean CommissionJunta de AndalucíaFundación Mari Paz Jiménez CasadoFundación CRIS contra el CáncerAsociación Pablo UgarteFundación María García EstradaGrupo GEISCentro de Investigación Biomédica en Red Cáncer (España)Universidad de SevillaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcPublisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/306808https://api.elsevier.com/content/abstract/scopus_id/85144928549reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI//IJC-2018-036767-Ihttps://doi.org/10.3390/cancers14246211Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3068082026-05-22T06:33:51Z
dc.title.none.fl_str_mv Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma
title Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma
spellingShingle Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma
Salguero-Aranda, Carmen
Sarcoma
Hippo pathway
TAZ
YAP
Gene fusions
title_short Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma
title_full Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma
title_fullStr Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma
title_full_unstemmed Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma
title_sort Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma
dc.creator.none.fl_str_mv Salguero-Aranda, Carmen
Olmedo-Pelayo, Joaquín
Álava, Enrique de
Amaral, Ana Teresa
Díaz-Martín, J.
author Salguero-Aranda, Carmen
author_facet Salguero-Aranda, Carmen
Olmedo-Pelayo, Joaquín
Álava, Enrique de
Amaral, Ana Teresa
Díaz-Martín, J.
author_role author
author2 Olmedo-Pelayo, Joaquín
Álava, Enrique de
Amaral, Ana Teresa
Díaz-Martín, J.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
European Commission
Junta de Andalucía
Fundación Mari Paz Jiménez Casado
Fundación CRIS contra el Cáncer
Asociación Pablo Ugarte
Fundación María García Estrada
Grupo GEIS
Centro de Investigación Biomédica en Red Cáncer (España)
Universidad de Sevilla
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Sarcoma
Hippo pathway
TAZ
YAP
Gene fusions
topic Sarcoma
Hippo pathway
TAZ
YAP
Gene fusions
description The Hippo pathway is an evolutionarily conserved modulator of developmental biology with a key role in tissue and organ size regulation under homeostatic conditions. Like other signaling pathways with a significant role in embryonic development, the deregulation of Hippo signaling contributes to oncogenesis. Central to the Hippo pathway is a conserved cascade of adaptor proteins and inhibitory kinases that converge and regulate the activity of the oncoproteins YAP and TAZ, the final transducers of the pathway. Elevated levels and aberrant activation of YAP and TAZ have been described in many cancers. Though most of the studies describe their pervasive activation in epithelial neoplasms, there is increasing evidence pointing out its relevance in mesenchymal malignancies as well. Interestingly, somatic or germline mutations in genes of the Hippo pathway are scarce compared to other signaling pathways that are frequently disrupted in cancer. However, in the case of sarcomas, several examples of genetic alteration of Hippo members, including gene fusions, have been described during the last few years. Here, we review the current knowledge of Hippo pathway implication in sarcoma, describing mechanistic hints recently reported in specific histological entities and how these alterations represent an opportunity for targeted therapy in this heterogeneous group of neoplasm.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_dcae04bc
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/306808
https://api.elsevier.com/content/abstract/scopus_id/85144928549
url http://hdl.handle.net/10261/306808
https://api.elsevier.com/content/abstract/scopus_id/85144928549
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI//IJC-2018-036767-I
https://doi.org/10.3390/cancers14246211
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406311218675712
score 15,812429

Registros relacionados