β3 integrin expression is required for invadopodia-mediated ECM degradation in lung carcinoma cells.

Cancer related deaths are primarily due to tumor metastasis. To facilitate their dissemination to distant sites, cancer cells develop invadopodia, actin-rich protrusions capable of degrading the surrounding extracellular matrix (ECM). We aimed to determine whether β3 integrin participates in invadop...

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Main Authors: Rafael Peláez, Xabier Morales, Elizabeth Salvo, Saray Garasa, Carlos Ortiz de Solórzano, Alfredo Martínez, Ignacio M Larrayoz, Ana Rouzaut
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5540285?pdf=render
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author Rafael Peláez
Xabier Morales
Elizabeth Salvo
Saray Garasa
Carlos Ortiz de Solórzano
Alfredo Martínez
Ignacio M Larrayoz
Ana Rouzaut
author_facet Rafael Peláez
Xabier Morales
Elizabeth Salvo
Saray Garasa
Carlos Ortiz de Solórzano
Alfredo Martínez
Ignacio M Larrayoz
Ana Rouzaut
author_sort Rafael Peláez
collection DOAJ
description Cancer related deaths are primarily due to tumor metastasis. To facilitate their dissemination to distant sites, cancer cells develop invadopodia, actin-rich protrusions capable of degrading the surrounding extracellular matrix (ECM). We aimed to determine whether β3 integrin participates in invadopodia formed by lung carcinoma cells, based on our previous findings of specific TGF-β induction of β3 integrin dependent metastasis in animal models of lung carcinoma. In this study, we demonstrate that lung carcinoma cells form invadopodia in response to TGF-β exposure. Invadopodia formation and degradation activity is dependent on β3 integrin expression since β3 integrin deficient cells are not able to degrade gelatin-coated surfaces. Even more, transient over-expression of SRC did not restore invadopodia formation in β3 integrin deficient cells. Finally, we observed that blockade of PLC-dependent signaling leads to more intense labeling for β3 integrin in invadopodia. Our results suggest that β3 integrin function, and location, in lung cancer cells are essential for invadopodia formation, and this integrin regulates the activation of different signal pathways necessary for the invasive structure. β3 integrin has been associated with poor prognosis and increased metastasis in several carcinoma types, including lung cancer. Our findings provide new evidence to support the use of targeted therapies against this integrin to combat the onset of metastases.
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spelling doaj.art-78ad314655c94e2bb6e3b33cb32d6ba72022-12-22T03:54:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018157910.1371/journal.pone.0181579β3 integrin expression is required for invadopodia-mediated ECM degradation in lung carcinoma cells.Rafael PeláezXabier MoralesElizabeth SalvoSaray GarasaCarlos Ortiz de SolórzanoAlfredo MartínezIgnacio M LarrayozAna RouzautCancer related deaths are primarily due to tumor metastasis. To facilitate their dissemination to distant sites, cancer cells develop invadopodia, actin-rich protrusions capable of degrading the surrounding extracellular matrix (ECM). We aimed to determine whether β3 integrin participates in invadopodia formed by lung carcinoma cells, based on our previous findings of specific TGF-β induction of β3 integrin dependent metastasis in animal models of lung carcinoma. In this study, we demonstrate that lung carcinoma cells form invadopodia in response to TGF-β exposure. Invadopodia formation and degradation activity is dependent on β3 integrin expression since β3 integrin deficient cells are not able to degrade gelatin-coated surfaces. Even more, transient over-expression of SRC did not restore invadopodia formation in β3 integrin deficient cells. Finally, we observed that blockade of PLC-dependent signaling leads to more intense labeling for β3 integrin in invadopodia. Our results suggest that β3 integrin function, and location, in lung cancer cells are essential for invadopodia formation, and this integrin regulates the activation of different signal pathways necessary for the invasive structure. β3 integrin has been associated with poor prognosis and increased metastasis in several carcinoma types, including lung cancer. Our findings provide new evidence to support the use of targeted therapies against this integrin to combat the onset of metastases.http://europepmc.org/articles/PMC5540285?pdf=render
spellingShingle Rafael Peláez
Xabier Morales
Elizabeth Salvo
Saray Garasa
Carlos Ortiz de Solórzano
Alfredo Martínez
Ignacio M Larrayoz
Ana Rouzaut
β3 integrin expression is required for invadopodia-mediated ECM degradation in lung carcinoma cells.
PLoS ONE
title β3 integrin expression is required for invadopodia-mediated ECM degradation in lung carcinoma cells.
title_full β3 integrin expression is required for invadopodia-mediated ECM degradation in lung carcinoma cells.
title_fullStr β3 integrin expression is required for invadopodia-mediated ECM degradation in lung carcinoma cells.
title_full_unstemmed β3 integrin expression is required for invadopodia-mediated ECM degradation in lung carcinoma cells.
title_short β3 integrin expression is required for invadopodia-mediated ECM degradation in lung carcinoma cells.
title_sort β3 integrin expression is required for invadopodia mediated ecm degradation in lung carcinoma cells
url http://europepmc.org/articles/PMC5540285?pdf=render
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