HGK promotes metastatic dissemination in prostate cancer

Metastasis is the process of cancer cell dissemination from primary tumors to different organs being the bone the preferred site for metastatic homing of prostate cancer (PCa) cells. Prostate tumorigenesis is a multi stage process that ultimately tends to advance to become metastatic PCa. Once PCa p...

Descripción completa

Detalles Bibliográficos
Autores: Bragado Domingo, Paloma, Porras Gallo, María Almudena, Gutiérrez Uzquiza, Álvaro, Garcia-Garcia, Sara, Rodrigo-Faus, Maria, Fonseca, Noelia, Manzano, Sara, Győrffy, Balázs, Ocaña, Alberto
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/114760
Acceso en línea:https://hdl.handle.net/20.500.14352/114760
Access Level:acceso abierto
Palabra clave:616-006.64-092.18
616-006.04
Cancer de prostata
Metástasis
Oncología
2302 Bioquímica
id ES_0a4668be0675ffba249eb10e2f0ebae5
oai_identifier_str oai:docta.ucm.es:20.500.14352/114760
network_acronym_str ES
network_name_str España
repository_id_str
spelling HGK promotes metastatic dissemination in prostate cancerBragado Domingo, PalomaPorras Gallo, María AlmudenaGutiérrez Uzquiza, ÁlvaroGarcia-Garcia, SaraRodrigo-Faus, MariaFonseca, NoeliaManzano, SaraGyőrffy, BalázsOcaña, Alberto616-006.64-092.18616-006.04Cancer de prostataMetástasisOncología2302 BioquímicaMetastasis is the process of cancer cell dissemination from primary tumors to different organs being the bone the preferred site for metastatic homing of prostate cancer (PCa) cells. Prostate tumorigenesis is a multi stage process that ultimately tends to advance to become metastatic PCa. Once PCa patients develop skeletal metastases, they eventually succumb to the disease. Therefore, it is imperative to identify essential molecular drivers of this process to develop new therapeutic alternatives for the treatment of this devastating disease. Here, we have identified MAP4K4 as a relevant gene for metastasis in PCa. Our work shows that genetic deletion of MAP4K4 or pharmacological inhibition of its encoded kinase, HGK, inhibits metastatic PCa cells migration and clonogenic properties. Hence, MAP4K4 might promote metastasis and tumor growth. Mechanistically, our results indicate that HGK depleted cells exhibit profound differences in F actin organization, increasing cell spreading and focal adhesion stability. Additionally, HGK depleted cells fails to respond to TNF α stimulation and chemoattractant action. Moreover, here we show that HGK upregulation in PCa samples from TCGA and other databases correlates with a poor prognosis of the disease. Hence, we suggest that it could be used as prognostic biomarker to predict the appearance of an aggressive phenotype of PCa tumors and ultimately, the appearance of metastasis. In summary, our results highlight an essential role for HGK in the dissemination of PCa cells and its potential use as prognostic biomarker.Nature PorfolioUniversidad Complutense de Madrid20212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/114760reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1147602026-06-02T12:44:21Z
dc.title.none.fl_str_mv HGK promotes metastatic dissemination in prostate cancer
title HGK promotes metastatic dissemination in prostate cancer
spellingShingle HGK promotes metastatic dissemination in prostate cancer
Bragado Domingo, Paloma
616-006.64-092.18
616-006.04
Cancer de prostata
Metástasis
Oncología
2302 Bioquímica
title_short HGK promotes metastatic dissemination in prostate cancer
title_full HGK promotes metastatic dissemination in prostate cancer
title_fullStr HGK promotes metastatic dissemination in prostate cancer
title_full_unstemmed HGK promotes metastatic dissemination in prostate cancer
title_sort HGK promotes metastatic dissemination in prostate cancer
dc.creator.none.fl_str_mv Bragado Domingo, Paloma
Porras Gallo, María Almudena
Gutiérrez Uzquiza, Álvaro
Garcia-Garcia, Sara
Rodrigo-Faus, Maria
Fonseca, Noelia
Manzano, Sara
Győrffy, Balázs
Ocaña, Alberto
author Bragado Domingo, Paloma
author_facet Bragado Domingo, Paloma
Porras Gallo, María Almudena
Gutiérrez Uzquiza, Álvaro
Garcia-Garcia, Sara
Rodrigo-Faus, Maria
Fonseca, Noelia
Manzano, Sara
Győrffy, Balázs
Ocaña, Alberto
author_role author
author2 Porras Gallo, María Almudena
Gutiérrez Uzquiza, Álvaro
Garcia-Garcia, Sara
Rodrigo-Faus, Maria
Fonseca, Noelia
Manzano, Sara
Győrffy, Balázs
Ocaña, Alberto
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 616-006.64-092.18
616-006.04
Cancer de prostata
Metástasis
Oncología
2302 Bioquímica
topic 616-006.64-092.18
616-006.04
Cancer de prostata
Metástasis
Oncología
2302 Bioquímica
description Metastasis is the process of cancer cell dissemination from primary tumors to different organs being the bone the preferred site for metastatic homing of prostate cancer (PCa) cells. Prostate tumorigenesis is a multi stage process that ultimately tends to advance to become metastatic PCa. Once PCa patients develop skeletal metastases, they eventually succumb to the disease. Therefore, it is imperative to identify essential molecular drivers of this process to develop new therapeutic alternatives for the treatment of this devastating disease. Here, we have identified MAP4K4 as a relevant gene for metastasis in PCa. Our work shows that genetic deletion of MAP4K4 or pharmacological inhibition of its encoded kinase, HGK, inhibits metastatic PCa cells migration and clonogenic properties. Hence, MAP4K4 might promote metastasis and tumor growth. Mechanistically, our results indicate that HGK depleted cells exhibit profound differences in F actin organization, increasing cell spreading and focal adhesion stability. Additionally, HGK depleted cells fails to respond to TNF α stimulation and chemoattractant action. Moreover, here we show that HGK upregulation in PCa samples from TCGA and other databases correlates with a poor prognosis of the disease. Hence, we suggest that it could be used as prognostic biomarker to predict the appearance of an aggressive phenotype of PCa tumors and ultimately, the appearance of metastasis. In summary, our results highlight an essential role for HGK in the dissemination of PCa cells and its potential use as prognostic biomarker.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/114760
url https://hdl.handle.net/20.500.14352/114760
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Porfolio
publisher.none.fl_str_mv Nature Porfolio
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869403154388353024
score 15,812429

Similares en LA Referencia