Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway

Abstract We have previously shown that the transmembrane protein ODZ1 serves for glioblastoma (GBM) cells to invade the surrounding tissue through activation of RhoA/ROCK pathway. However, the transcriptional machinery used by GBM cells to regulate the expression of ODZ1 is unknown. Here we show tha...

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Autores principales:	Veronica Vidal, Olga Gutierrez, Ana Talamillo, Carlos Velasquez, Jose L. Fernandez-Luna
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9da1ef457508437ea7261509bcb8286d
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spelling	oai:doaj.org-article:9da1ef457508437ea7261509bcb8286d2021-12-02T18:51:01ZGlioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway10.1038/s41598-021-95753-62045-2322https://doaj.org/article/9da1ef457508437ea7261509bcb8286d2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95753-6https://doaj.org/toc/2045-2322Abstract We have previously shown that the transmembrane protein ODZ1 serves for glioblastoma (GBM) cells to invade the surrounding tissue through activation of RhoA/ROCK pathway. However, the transcriptional machinery used by GBM cells to regulate the expression of ODZ1 is unknown. Here we show that interaction with tumor microenvironment elements, mainly activated monocytes through IL-6 secretion, and the extracellular matrix protein fibronectin, induces the Stat3 transcriptional pathway and upregulates ODZ1 which results in GBM cell migration. This signaling route is abrogated by blocking the IL-6 receptor, inhibiting Jak kinases or knocking down Stat3. Furthermore, we have identified a Stat3 responsive element in the ODZ1 gene promoter, about 1 kb from the transcription start site. Luciferase-reporter assays confirmed that the promoter responds to the presence of monocytic cells and this activation is greatly reduced when the Stat3 site is mutated or following treatment with a neutralizing anti-IL-6 receptor antibody or transfecting GBM cells with a dominant negative variant of Stat3. Overall, we show that monocyte-secreted IL-6 and the extracellular matrix protein fibronectin activate the axis Stat3-ODZ1 and promote migration of GBM cells. This is the first described transcriptional mechanism used by tumor cells to promote the expression of the invasion factor ODZ1.Veronica VidalOlga GutierrezAna TalamilloCarlos VelasquezJose L. Fernandez-LunaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Veronica Vidal Olga Gutierrez Ana Talamillo Carlos Velasquez Jose L. Fernandez-Luna Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway
description	Abstract We have previously shown that the transmembrane protein ODZ1 serves for glioblastoma (GBM) cells to invade the surrounding tissue through activation of RhoA/ROCK pathway. However, the transcriptional machinery used by GBM cells to regulate the expression of ODZ1 is unknown. Here we show that interaction with tumor microenvironment elements, mainly activated monocytes through IL-6 secretion, and the extracellular matrix protein fibronectin, induces the Stat3 transcriptional pathway and upregulates ODZ1 which results in GBM cell migration. This signaling route is abrogated by blocking the IL-6 receptor, inhibiting Jak kinases or knocking down Stat3. Furthermore, we have identified a Stat3 responsive element in the ODZ1 gene promoter, about 1 kb from the transcription start site. Luciferase-reporter assays confirmed that the promoter responds to the presence of monocytic cells and this activation is greatly reduced when the Stat3 site is mutated or following treatment with a neutralizing anti-IL-6 receptor antibody or transfecting GBM cells with a dominant negative variant of Stat3. Overall, we show that monocyte-secreted IL-6 and the extracellular matrix protein fibronectin activate the axis Stat3-ODZ1 and promote migration of GBM cells. This is the first described transcriptional mechanism used by tumor cells to promote the expression of the invasion factor ODZ1.
format	article
author	Veronica Vidal Olga Gutierrez Ana Talamillo Carlos Velasquez Jose L. Fernandez-Luna
author_facet	Veronica Vidal Olga Gutierrez Ana Talamillo Carlos Velasquez Jose L. Fernandez-Luna
author_sort	Veronica Vidal
title	Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway
title_short	Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway
title_full	Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway
title_fullStr	Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway
title_full_unstemmed	Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway
title_sort	glioblastoma invasion factor odz1 is induced by microenvironmental signals through activation of a stat3-dependent transcriptional pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9da1ef457508437ea7261509bcb8286d
work_keys_str_mv	AT veronicavidal glioblastomainvasionfactorodz1isinducedbymicroenvironmentalsignalsthroughactivationofastat3dependenttranscriptionalpathway AT olgagutierrez glioblastomainvasionfactorodz1isinducedbymicroenvironmentalsignalsthroughactivationofastat3dependenttranscriptionalpathway AT anatalamillo glioblastomainvasionfactorodz1isinducedbymicroenvironmentalsignalsthroughactivationofastat3dependenttranscriptionalpathway AT carlosvelasquez glioblastomainvasionfactorodz1isinducedbymicroenvironmentalsignalsthroughactivationofastat3dependenttranscriptionalpathway AT joselfernandezluna glioblastomainvasionfactorodz1isinducedbymicroenvironmentalsignalsthroughactivationofastat3dependenttranscriptionalpathway
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Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway

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