HGK promotes metastatic dissemination in prostate cancer

Abstract 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. O...

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Autores principales:	Sara Garcia-Garcia, Maria Rodrigo-Faus, Noelia Fonseca, Sara Manzano, Balázs Győrffy, Alberto Ocaña, Paloma Bragado, Almudena Porras, Alvaro Gutierrez-Uzquiza
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8f492cc077af4106be60cc15dc54728d
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spelling	oai:doaj.org-article:8f492cc077af4106be60cc15dc54728d2021-12-02T17:47:23ZHGK promotes metastatic dissemination in prostate cancer10.1038/s41598-021-91292-22045-2322https://doaj.org/article/8f492cc077af4106be60cc15dc54728d2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91292-2https://doaj.org/toc/2045-2322Abstract 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.Sara Garcia-GarciaMaria Rodrigo-FausNoelia FonsecaSara ManzanoBalázs GyőrffyAlberto OcañaPaloma BragadoAlmudena PorrasAlvaro Gutierrez-UzquizaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sara Garcia-Garcia Maria Rodrigo-Faus Noelia Fonseca Sara Manzano Balázs Győrffy Alberto Ocaña Paloma Bragado Almudena Porras Alvaro Gutierrez-Uzquiza HGK promotes metastatic dissemination in prostate cancer
description	Abstract 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.
format	article
author	Sara Garcia-Garcia Maria Rodrigo-Faus Noelia Fonseca Sara Manzano Balázs Győrffy Alberto Ocaña Paloma Bragado Almudena Porras Alvaro Gutierrez-Uzquiza
author_facet	Sara Garcia-Garcia Maria Rodrigo-Faus Noelia Fonseca Sara Manzano Balázs Győrffy Alberto Ocaña Paloma Bragado Almudena Porras Alvaro Gutierrez-Uzquiza
author_sort	Sara Garcia-Garcia
title	HGK promotes metastatic dissemination in prostate cancer
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
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8f492cc077af4106be60cc15dc54728d
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HGK promotes metastatic dissemination in prostate cancer

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