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Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion

Invasive cancer cells form dynamic adhesive structures associated with matrix degradation called invadopodia. Calpain 2 is a calcium-dependent intracellular protease that regulates adhesion turnover and disassembly through the targeting of specific substrates such as talin. Here, we describe a novel...

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Autores principales: Cortesio, Christa L., Chan, Keefe T., Perrin, Benjamin J., Burton, Nicholas O., Zhang, Sheng, Zhang, Zhong-Yin, Huttenlocher, Anna
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265405/
https://www.ncbi.nlm.nih.gov/pubmed/18332219
http://dx.doi.org/10.1083/jcb.200708048
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author Cortesio, Christa L.
Chan, Keefe T.
Perrin, Benjamin J.
Burton, Nicholas O.
Zhang, Sheng
Zhang, Zhong-Yin
Huttenlocher, Anna
author_facet Cortesio, Christa L.
Chan, Keefe T.
Perrin, Benjamin J.
Burton, Nicholas O.
Zhang, Sheng
Zhang, Zhong-Yin
Huttenlocher, Anna
author_sort Cortesio, Christa L.
collection PubMed
description Invasive cancer cells form dynamic adhesive structures associated with matrix degradation called invadopodia. Calpain 2 is a calcium-dependent intracellular protease that regulates adhesion turnover and disassembly through the targeting of specific substrates such as talin. Here, we describe a novel function for calpain 2 in the formation of invadopodia and in the invasive abilities of breast cancer cells through the modulation of endogenous c-Src activity. Calpain-deficient breast cancer cells show impaired invadopodia formation that is rescued by expression of a truncated fragment of protein tyrosine phosphatase 1B (PTP1B) corresponding to the calpain proteolytic fragment, which indicates that calpain modulates invadopodia through PTP1B. Moreover, PTP1B activity is required for efficient invadopodia formation and breast cancer invasion, which suggests that PTP1B may modulate breast cancer progression through its effects on invadopodia. Collectively, our experiments implicate a novel signaling pathway involving calpain 2, PTP1B, and Src in the regulation of invadopodia and breast cancer invasion.
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spelling pubmed-22654052008-09-10 Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion Cortesio, Christa L. Chan, Keefe T. Perrin, Benjamin J. Burton, Nicholas O. Zhang, Sheng Zhang, Zhong-Yin Huttenlocher, Anna J Cell Biol Research Articles Invasive cancer cells form dynamic adhesive structures associated with matrix degradation called invadopodia. Calpain 2 is a calcium-dependent intracellular protease that regulates adhesion turnover and disassembly through the targeting of specific substrates such as talin. Here, we describe a novel function for calpain 2 in the formation of invadopodia and in the invasive abilities of breast cancer cells through the modulation of endogenous c-Src activity. Calpain-deficient breast cancer cells show impaired invadopodia formation that is rescued by expression of a truncated fragment of protein tyrosine phosphatase 1B (PTP1B) corresponding to the calpain proteolytic fragment, which indicates that calpain modulates invadopodia through PTP1B. Moreover, PTP1B activity is required for efficient invadopodia formation and breast cancer invasion, which suggests that PTP1B may modulate breast cancer progression through its effects on invadopodia. Collectively, our experiments implicate a novel signaling pathway involving calpain 2, PTP1B, and Src in the regulation of invadopodia and breast cancer invasion. The Rockefeller University Press 2008-03-10 /pmc/articles/PMC2265405/ /pubmed/18332219 http://dx.doi.org/10.1083/jcb.200708048 Text en Copyright © 2008, The Rockefeller University Press 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 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Cortesio, Christa L.
Chan, Keefe T.
Perrin, Benjamin J.
Burton, Nicholas O.
Zhang, Sheng
Zhang, Zhong-Yin
Huttenlocher, Anna
Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion
title Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion
title_full Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion
title_fullStr Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion
title_full_unstemmed Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion
title_short Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion
title_sort calpain 2 and ptp1b function in a novel pathway with src to regulate invadopodia dynamics and breast cancer cell invasion
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265405/
https://www.ncbi.nlm.nih.gov/pubmed/18332219
http://dx.doi.org/10.1083/jcb.200708048
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