Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2

Abstract Hypoxia is a common feature of solid tumours that promotes invasion and metastatic dissemination. Invadopodia are actin-rich membrane protrusions that direct extracellular matrix proteolysis and facilitate tumour cell invasion. Here, we show that CSRP2, an invadopodial actin bundling protei...

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Autores principales:	Céline Hoffmann, Xianqing Mao, Joshua Brown-Clay, Flora Moreau, Antoun Al Absi, Hannah Wurzer, Barbara Sousa, Fernando Schmitt, Guy Berchem, Bassam Janji, Clément Thomas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9aa369442f8843179906f34893c25651
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spelling	oai:doaj.org-article:9aa369442f8843179906f34893c256512021-12-02T15:08:16ZHypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP210.1038/s41598-018-28637-x2045-2322https://doaj.org/article/9aa369442f8843179906f34893c256512018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28637-xhttps://doaj.org/toc/2045-2322Abstract Hypoxia is a common feature of solid tumours that promotes invasion and metastatic dissemination. Invadopodia are actin-rich membrane protrusions that direct extracellular matrix proteolysis and facilitate tumour cell invasion. Here, we show that CSRP2, an invadopodial actin bundling protein, is upregulated by hypoxia in various breast cancer cell lines, as well as in pre-clinical and clinical breast tumour specimens. We functionally characterized two hypoxia responsive elements within the proximal promoter of CSRP2 gene which are targeted by hypoxia-inducible factor-1 (HIF-1) and required for promoter transactivation in response to hypoxia. Remarkably, CSRP2 knockdown significantly inhibits hypoxia-stimulated invadopodium formation, ECM degradation and invasion in MDA-MB-231 cells, while CSRP2 forced expression was sufficient to enhance the invasive capacity of HIF-1α-depleted cells under hypoxia. In MCF-7 cells, CSRP2 upregulation was required for hypoxia-induced formation of invadopodium precursors that were unable to promote ECM degradation. Collectively, our data support that CSRP2 is a novel and direct cytoskeletal target of HIF-1 which facilitates hypoxia-induced breast cancer cell invasion by promoting invadopodia formation.Céline HoffmannXianqing MaoJoshua Brown-ClayFlora MoreauAntoun Al AbsiHannah WurzerBarbara SousaFernando SchmittGuy BerchemBassam JanjiClément ThomasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Céline Hoffmann Xianqing Mao Joshua Brown-Clay Flora Moreau Antoun Al Absi Hannah Wurzer Barbara Sousa Fernando Schmitt Guy Berchem Bassam Janji Clément Thomas Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2
description	Abstract Hypoxia is a common feature of solid tumours that promotes invasion and metastatic dissemination. Invadopodia are actin-rich membrane protrusions that direct extracellular matrix proteolysis and facilitate tumour cell invasion. Here, we show that CSRP2, an invadopodial actin bundling protein, is upregulated by hypoxia in various breast cancer cell lines, as well as in pre-clinical and clinical breast tumour specimens. We functionally characterized two hypoxia responsive elements within the proximal promoter of CSRP2 gene which are targeted by hypoxia-inducible factor-1 (HIF-1) and required for promoter transactivation in response to hypoxia. Remarkably, CSRP2 knockdown significantly inhibits hypoxia-stimulated invadopodium formation, ECM degradation and invasion in MDA-MB-231 cells, while CSRP2 forced expression was sufficient to enhance the invasive capacity of HIF-1α-depleted cells under hypoxia. In MCF-7 cells, CSRP2 upregulation was required for hypoxia-induced formation of invadopodium precursors that were unable to promote ECM degradation. Collectively, our data support that CSRP2 is a novel and direct cytoskeletal target of HIF-1 which facilitates hypoxia-induced breast cancer cell invasion by promoting invadopodia formation.
format	article
author	Céline Hoffmann Xianqing Mao Joshua Brown-Clay Flora Moreau Antoun Al Absi Hannah Wurzer Barbara Sousa Fernando Schmitt Guy Berchem Bassam Janji Clément Thomas
author_facet	Céline Hoffmann Xianqing Mao Joshua Brown-Clay Flora Moreau Antoun Al Absi Hannah Wurzer Barbara Sousa Fernando Schmitt Guy Berchem Bassam Janji Clément Thomas
author_sort	Céline Hoffmann
title	Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2
title_short	Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2
title_full	Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2
title_fullStr	Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2
title_full_unstemmed	Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2
title_sort	hypoxia promotes breast cancer cell invasion through hif-1α-mediated up-regulation of the invadopodial actin bundling protein csrp2
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/9aa369442f8843179906f34893c25651
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Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2

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