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Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1

The process by which tumor cells mechanically invade through surrounding stroma into peripheral tissues is an essential component of metastatic dissemination. The directed recruitment of the metalloproteinase MT1-MMP to invadopodia plays a critical role in this invasive process. Here, we provide mec...

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Autores principales: Qiang, Li, Cao, Hong, Chen, Jing, Weller, Shaun G., Krueger, Eugene W., Zhang, Lizhi, Razidlo, Gina L., McNiven, Mark A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314558/
https://www.ncbi.nlm.nih.gov/pubmed/30487181
http://dx.doi.org/10.1083/jcb.201802032
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author Qiang, Li
Cao, Hong
Chen, Jing
Weller, Shaun G.
Krueger, Eugene W.
Zhang, Lizhi
Razidlo, Gina L.
McNiven, Mark A.
author_facet Qiang, Li
Cao, Hong
Chen, Jing
Weller, Shaun G.
Krueger, Eugene W.
Zhang, Lizhi
Razidlo, Gina L.
McNiven, Mark A.
author_sort Qiang, Li
collection PubMed
description The process by which tumor cells mechanically invade through surrounding stroma into peripheral tissues is an essential component of metastatic dissemination. The directed recruitment of the metalloproteinase MT1-MMP to invadopodia plays a critical role in this invasive process. Here, we provide mechanistic insight into MT1-MMP cytoplasmic tail binding protein 1 (MTCBP-1) with respect to invadopodia formation, matrix remodeling, and invasion by pancreatic tumor cells. MTCBP-1 localizes to invadopodia and interacts with MT1-MMP. We find that this interaction displaces MT1-MMP from invadopodia, thereby attenuating their number and function and reducing the capacity of tumor cells to degrade matrix. Further, we observe an inverse correlation between MTCBP-1 and MT1-MMP expression both in cultured cell lines and human pancreatic tumors. Consistently, MTCBP-1–expressing cells show decreased ability to invade in vitro and metastasize in vivo. These findings implicate MTCBP-1 as an inhibitor of the metastatic process.
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spelling pubmed-63145582019-07-07 Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1 Qiang, Li Cao, Hong Chen, Jing Weller, Shaun G. Krueger, Eugene W. Zhang, Lizhi Razidlo, Gina L. McNiven, Mark A. J Cell Biol Research Articles The process by which tumor cells mechanically invade through surrounding stroma into peripheral tissues is an essential component of metastatic dissemination. The directed recruitment of the metalloproteinase MT1-MMP to invadopodia plays a critical role in this invasive process. Here, we provide mechanistic insight into MT1-MMP cytoplasmic tail binding protein 1 (MTCBP-1) with respect to invadopodia formation, matrix remodeling, and invasion by pancreatic tumor cells. MTCBP-1 localizes to invadopodia and interacts with MT1-MMP. We find that this interaction displaces MT1-MMP from invadopodia, thereby attenuating their number and function and reducing the capacity of tumor cells to degrade matrix. Further, we observe an inverse correlation between MTCBP-1 and MT1-MMP expression both in cultured cell lines and human pancreatic tumors. Consistently, MTCBP-1–expressing cells show decreased ability to invade in vitro and metastasize in vivo. These findings implicate MTCBP-1 as an inhibitor of the metastatic process. Rockefeller University Press 2019-01-07 /pmc/articles/PMC6314558/ /pubmed/30487181 http://dx.doi.org/10.1083/jcb.201802032 Text en © 2018 Qiang 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
Qiang, Li
Cao, Hong
Chen, Jing
Weller, Shaun G.
Krueger, Eugene W.
Zhang, Lizhi
Razidlo, Gina L.
McNiven, Mark A.
Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1
title Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1
title_full Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1
title_fullStr Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1
title_full_unstemmed Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1
title_short Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1
title_sort pancreatic tumor cell metastasis is restricted by mt1-mmp binding protein mtcbp-1
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314558/
https://www.ncbi.nlm.nih.gov/pubmed/30487181
http://dx.doi.org/10.1083/jcb.201802032
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