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SNX27–retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis

A variety of metastatic cancer cells use actin-rich membrane protrusions, known as invadopodia, for efficient ECM degradation, which involves trafficking of proteases from intracellular compartments to these structures. Here, we demonstrate that in the metastatic breast cancer cell line MDA-MB-231,...

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Autores principales: Sharma, Priyanka, Parveen, Sameena, Shah, Lekha V., Mukherjee, Madhumita, Kalaidzidis, Yannis, Kozielski, Anthony J., Rosato, Roberto, Chang, Jenny C., Datta, Sunando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039210/
https://www.ncbi.nlm.nih.gov/pubmed/31820782
http://dx.doi.org/10.1083/jcb.201812098
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author Sharma, Priyanka
Parveen, Sameena
Shah, Lekha V.
Mukherjee, Madhumita
Kalaidzidis, Yannis
Kozielski, Anthony J.
Rosato, Roberto
Chang, Jenny C.
Datta, Sunando
author_facet Sharma, Priyanka
Parveen, Sameena
Shah, Lekha V.
Mukherjee, Madhumita
Kalaidzidis, Yannis
Kozielski, Anthony J.
Rosato, Roberto
Chang, Jenny C.
Datta, Sunando
author_sort Sharma, Priyanka
collection PubMed
description A variety of metastatic cancer cells use actin-rich membrane protrusions, known as invadopodia, for efficient ECM degradation, which involves trafficking of proteases from intracellular compartments to these structures. Here, we demonstrate that in the metastatic breast cancer cell line MDA-MB-231, retromer regulates the matrix invasion activity by recycling matrix metalloprotease, MT1-MMP. We further found that MT2-MMP, another abundantly expressed metalloprotease, is also invadopodia associated. MT1- and MT2-MMP showed a high degree of colocalization but were located on the distinct endosomal domains. Retromer and its associated sorting nexin, SNX27, phenocopied each other in matrix degradation via selectively recycling MT1-MMP but not MT2-MMP. ITC-based studies revealed that both SNX27 and retromer could directly interact with MT1-MMP. Analysis from a publicly available database showed SNX27 to be overexpressed or frequently altered in the patients having invasive breast cancer. In xenograft-based studies, SNX27-depleted cell lines showed prolonged survival of SCID mice, suggesting a possible implication for overexpression of the sorting nexin in tumor samples.
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spelling pubmed-70392102020-07-06 SNX27–retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis Sharma, Priyanka Parveen, Sameena Shah, Lekha V. Mukherjee, Madhumita Kalaidzidis, Yannis Kozielski, Anthony J. Rosato, Roberto Chang, Jenny C. Datta, Sunando J Cell Biol Research Articles A variety of metastatic cancer cells use actin-rich membrane protrusions, known as invadopodia, for efficient ECM degradation, which involves trafficking of proteases from intracellular compartments to these structures. Here, we demonstrate that in the metastatic breast cancer cell line MDA-MB-231, retromer regulates the matrix invasion activity by recycling matrix metalloprotease, MT1-MMP. We further found that MT2-MMP, another abundantly expressed metalloprotease, is also invadopodia associated. MT1- and MT2-MMP showed a high degree of colocalization but were located on the distinct endosomal domains. Retromer and its associated sorting nexin, SNX27, phenocopied each other in matrix degradation via selectively recycling MT1-MMP but not MT2-MMP. ITC-based studies revealed that both SNX27 and retromer could directly interact with MT1-MMP. Analysis from a publicly available database showed SNX27 to be overexpressed or frequently altered in the patients having invasive breast cancer. In xenograft-based studies, SNX27-depleted cell lines showed prolonged survival of SCID mice, suggesting a possible implication for overexpression of the sorting nexin in tumor samples. Rockefeller University Press 2019-12-09 /pmc/articles/PMC7039210/ /pubmed/31820782 http://dx.doi.org/10.1083/jcb.201812098 Text en © 2019 Sharma et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Sharma, Priyanka
Parveen, Sameena
Shah, Lekha V.
Mukherjee, Madhumita
Kalaidzidis, Yannis
Kozielski, Anthony J.
Rosato, Roberto
Chang, Jenny C.
Datta, Sunando
SNX27–retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis
title SNX27–retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis
title_full SNX27–retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis
title_fullStr SNX27–retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis
title_full_unstemmed SNX27–retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis
title_short SNX27–retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis
title_sort snx27–retromer assembly recycles mt1-mmp to invadopodia and promotes breast cancer metastasis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039210/
https://www.ncbi.nlm.nih.gov/pubmed/31820782
http://dx.doi.org/10.1083/jcb.201812098
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