Hakai overexpression effectively induces tumour progression and metastasis in vivo

Abstract At early stages of carcinoma progression, epithelial cells undergo a program named epithelial-to-mesenchymal transition characterized by the loss of the major component of the adherens junctions, E-cadherin, which in consequence causes the disruption of cell-cell contacts. Hakai is an E3 ub...

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Autores principales:	Raquel Castosa, Olaia Martinez-Iglesias, Daniel Roca-Lema, Alba Casas-Pais, Andrea Díaz-Díaz, Pilar Iglesias, Isabel Santamarina, Begoña Graña, Lourdes Calvo, Manuel Valladares-Ayerbes, Ángel Concha, Angélica Figueroa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2673c8d402fa48a18d278383f492cfe5
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spelling	oai:doaj.org-article:2673c8d402fa48a18d278383f492cfe52021-12-02T15:09:06ZHakai overexpression effectively induces tumour progression and metastasis in vivo10.1038/s41598-018-21808-w2045-2322https://doaj.org/article/2673c8d402fa48a18d278383f492cfe52018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21808-whttps://doaj.org/toc/2045-2322Abstract At early stages of carcinoma progression, epithelial cells undergo a program named epithelial-to-mesenchymal transition characterized by the loss of the major component of the adherens junctions, E-cadherin, which in consequence causes the disruption of cell-cell contacts. Hakai is an E3 ubiquitin-ligase that binds to E-cadherin in a phosphorylated-dependent manner and induces its degradation; thus modulating cell adhesions. Here, we show that Hakai expression is gradually increased in adenoma and in different TNM stages (I-IV) from colon adenocarcinomas compared to human colon healthy tissues. Moreover, we confirm that Hakai overexpression in epithelial cells drives transformation in cells, a mesenchymal and invasive phenotype, accompanied by the downregulation of E-cadherin and the upregulation of N-cadherin, and an increased proliferation and an oncogenic potential. More importantly, for the first time, we have studied the role of Hakai during cancer progression in vivo. We show that Hakai-transformed MDCK cells dramatically induce tumour growth and local invasion in nude mice and tumour cells exhibit a mesenchymal phenotype. Furthermore, we have detected the presence of micrometastasis in the lung mice, further confirming Hakai role during tumour metastasis in vivo. These results lead to the consideration of Hakai as a potential new therapeutic target to block tumour development and metastasis.Raquel CastosaOlaia Martinez-IglesiasDaniel Roca-LemaAlba Casas-PaisAndrea Díaz-DíazPilar IglesiasIsabel SantamarinaBegoña GrañaLourdes CalvoManuel Valladares-AyerbesÁngel ConchaAngélica FigueroaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Raquel Castosa Olaia Martinez-Iglesias Daniel Roca-Lema Alba Casas-Pais Andrea Díaz-Díaz Pilar Iglesias Isabel Santamarina Begoña Graña Lourdes Calvo Manuel Valladares-Ayerbes Ángel Concha Angélica Figueroa Hakai overexpression effectively induces tumour progression and metastasis in vivo
description	Abstract At early stages of carcinoma progression, epithelial cells undergo a program named epithelial-to-mesenchymal transition characterized by the loss of the major component of the adherens junctions, E-cadherin, which in consequence causes the disruption of cell-cell contacts. Hakai is an E3 ubiquitin-ligase that binds to E-cadherin in a phosphorylated-dependent manner and induces its degradation; thus modulating cell adhesions. Here, we show that Hakai expression is gradually increased in adenoma and in different TNM stages (I-IV) from colon adenocarcinomas compared to human colon healthy tissues. Moreover, we confirm that Hakai overexpression in epithelial cells drives transformation in cells, a mesenchymal and invasive phenotype, accompanied by the downregulation of E-cadherin and the upregulation of N-cadherin, and an increased proliferation and an oncogenic potential. More importantly, for the first time, we have studied the role of Hakai during cancer progression in vivo. We show that Hakai-transformed MDCK cells dramatically induce tumour growth and local invasion in nude mice and tumour cells exhibit a mesenchymal phenotype. Furthermore, we have detected the presence of micrometastasis in the lung mice, further confirming Hakai role during tumour metastasis in vivo. These results lead to the consideration of Hakai as a potential new therapeutic target to block tumour development and metastasis.
format	article
author	Raquel Castosa Olaia Martinez-Iglesias Daniel Roca-Lema Alba Casas-Pais Andrea Díaz-Díaz Pilar Iglesias Isabel Santamarina Begoña Graña Lourdes Calvo Manuel Valladares-Ayerbes Ángel Concha Angélica Figueroa
author_facet	Raquel Castosa Olaia Martinez-Iglesias Daniel Roca-Lema Alba Casas-Pais Andrea Díaz-Díaz Pilar Iglesias Isabel Santamarina Begoña Graña Lourdes Calvo Manuel Valladares-Ayerbes Ángel Concha Angélica Figueroa
author_sort	Raquel Castosa
title	Hakai overexpression effectively induces tumour progression and metastasis in vivo
title_short	Hakai overexpression effectively induces tumour progression and metastasis in vivo
title_full	Hakai overexpression effectively induces tumour progression and metastasis in vivo
title_fullStr	Hakai overexpression effectively induces tumour progression and metastasis in vivo
title_full_unstemmed	Hakai overexpression effectively induces tumour progression and metastasis in vivo
title_sort	hakai overexpression effectively induces tumour progression and metastasis in vivo
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/2673c8d402fa48a18d278383f492cfe5
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Hakai overexpression effectively induces tumour progression and metastasis in vivo

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