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CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis

A critical process underlying cancer metastasis is the acquisition by tumor cells of an invasive phenotype. At the subcellular level, invasion is facilitated by actin-rich protrusions termed invadopodia, which direct extracellular matrix (ECM) degradation. Here, we report the identification of a new...

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Autores principales: Hoffmann, Céline, Mao, Xianqing, Dieterle, Monika, Moreau, Flora, Al Absi, Antoun, Steinmetz, André, Oudin, Anaïs, Berchem, Guy, Janji, Bassam, Thomas, Clément
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924671/
https://www.ncbi.nlm.nih.gov/pubmed/26883198
http://dx.doi.org/10.18632/oncotarget.7327
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author Hoffmann, Céline
Mao, Xianqing
Dieterle, Monika
Moreau, Flora
Al Absi, Antoun
Steinmetz, André
Oudin, Anaïs
Berchem, Guy
Janji, Bassam
Thomas, Clément
author_facet Hoffmann, Céline
Mao, Xianqing
Dieterle, Monika
Moreau, Flora
Al Absi, Antoun
Steinmetz, André
Oudin, Anaïs
Berchem, Guy
Janji, Bassam
Thomas, Clément
author_sort Hoffmann, Céline
collection PubMed
description A critical process underlying cancer metastasis is the acquisition by tumor cells of an invasive phenotype. At the subcellular level, invasion is facilitated by actin-rich protrusions termed invadopodia, which direct extracellular matrix (ECM) degradation. Here, we report the identification of a new cytoskeletal component of breast cancer cell invadopodia, namely cysteine-rich protein 2 (CRP2). We found that CRP2 was not or only weakly expressed in epithelial breast cancer cells whereas it was up-regulated in mesenchymal/invasive breast cancer cells. In addition, high expression of the CRP2 encoding gene CSRP2 was associated with significantly increased risk of metastasis in basal-like breast cancer patients. CRP2 knockdown significantly reduced the invasive potential of aggressive breast cancer cells, whereas it did not impair 2D cell migration. In keeping with this, CRP2-depleted breast cancer cells exhibited a reduced capacity to promote ECM degradation, and to secrete and express MMP-9, a matrix metalloproteinase repeatedly associated with cancer progression and metastasis. In turn, ectopic expression of CRP2 in weakly invasive cells was sufficient to stimulate cell invasion. Both GFP-fused and endogenous CRP2 localized to the extended actin core of invadopodia, a structure primarily made of actin bundles. Purified recombinant CRP2 autonomously crosslinked actin filaments into thick bundles, suggesting that CRP2 contributes to the formation/maintenance of the actin core. Finally, CRP2 depletion significantly reduced the incidence of lung metastatic lesions in two xenograft mouse models of breast cancer. Collectively, our data identify CRP2 as a new cytoskeletal component of invadopodia that critically promotes breast cancer cell invasion and metastasis.
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spelling pubmed-49246712016-07-13 CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis Hoffmann, Céline Mao, Xianqing Dieterle, Monika Moreau, Flora Al Absi, Antoun Steinmetz, André Oudin, Anaïs Berchem, Guy Janji, Bassam Thomas, Clément Oncotarget Research Paper A critical process underlying cancer metastasis is the acquisition by tumor cells of an invasive phenotype. At the subcellular level, invasion is facilitated by actin-rich protrusions termed invadopodia, which direct extracellular matrix (ECM) degradation. Here, we report the identification of a new cytoskeletal component of breast cancer cell invadopodia, namely cysteine-rich protein 2 (CRP2). We found that CRP2 was not or only weakly expressed in epithelial breast cancer cells whereas it was up-regulated in mesenchymal/invasive breast cancer cells. In addition, high expression of the CRP2 encoding gene CSRP2 was associated with significantly increased risk of metastasis in basal-like breast cancer patients. CRP2 knockdown significantly reduced the invasive potential of aggressive breast cancer cells, whereas it did not impair 2D cell migration. In keeping with this, CRP2-depleted breast cancer cells exhibited a reduced capacity to promote ECM degradation, and to secrete and express MMP-9, a matrix metalloproteinase repeatedly associated with cancer progression and metastasis. In turn, ectopic expression of CRP2 in weakly invasive cells was sufficient to stimulate cell invasion. Both GFP-fused and endogenous CRP2 localized to the extended actin core of invadopodia, a structure primarily made of actin bundles. Purified recombinant CRP2 autonomously crosslinked actin filaments into thick bundles, suggesting that CRP2 contributes to the formation/maintenance of the actin core. Finally, CRP2 depletion significantly reduced the incidence of lung metastatic lesions in two xenograft mouse models of breast cancer. Collectively, our data identify CRP2 as a new cytoskeletal component of invadopodia that critically promotes breast cancer cell invasion and metastasis. Impact Journals LLC 2016-02-11 /pmc/articles/PMC4924671/ /pubmed/26883198 http://dx.doi.org/10.18632/oncotarget.7327 Text en Copyright: © 2016 Hoffmann et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Hoffmann, Céline
Mao, Xianqing
Dieterle, Monika
Moreau, Flora
Al Absi, Antoun
Steinmetz, André
Oudin, Anaïs
Berchem, Guy
Janji, Bassam
Thomas, Clément
CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis
title CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis
title_full CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis
title_fullStr CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis
title_full_unstemmed CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis
title_short CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis
title_sort crp2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924671/
https://www.ncbi.nlm.nih.gov/pubmed/26883198
http://dx.doi.org/10.18632/oncotarget.7327
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