MMP proteolytic activity regulates cancer invasiveness by modulating integrins

Abstract Cancer invasion through dense extracellular matrices (ECMs) is mediated by matrix metalloproteinases (MMPs) which degrade the ECM thereby creating paths for migration. However, how this degradation influences the phenotype of cancer cells is not fully clear. Here we address this question by...

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Autores principales: Alakesh Das, Melissa Monteiro, Amlan Barai, Sandeep Kumar, Shamik Sen
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/d3662dc961f54566b67919e8a216311e
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spelling oai:doaj.org-article:d3662dc961f54566b67919e8a216311e2021-12-02T15:05:09ZMMP proteolytic activity regulates cancer invasiveness by modulating integrins10.1038/s41598-017-14340-w2045-2322https://doaj.org/article/d3662dc961f54566b67919e8a216311e2017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-14340-whttps://doaj.org/toc/2045-2322Abstract Cancer invasion through dense extracellular matrices (ECMs) is mediated by matrix metalloproteinases (MMPs) which degrade the ECM thereby creating paths for migration. However, how this degradation influences the phenotype of cancer cells is not fully clear. Here we address this question by probing the function of MMPs in regulating biophysical properties of cancer cells relevant to invasion. We show that MMP catalytic activity regulates cell spreading, motility, contractility and cortical stiffness by stabilizing integrins at the membrane and activating focal adhesion kinase. Interestingly, cell rounding and cell softening on stiff gels induced by MMP inhibition is attenuated on MMP pre-conditioned surfaces. Together, our results suggest that MMP catalytic activity regulates invasiveness of cancer cells by modulating integrins.Alakesh DasMelissa MonteiroAmlan BaraiSandeep KumarShamik SenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Alakesh Das
Melissa Monteiro
Amlan Barai
Sandeep Kumar
Shamik Sen
MMP proteolytic activity regulates cancer invasiveness by modulating integrins
description Abstract Cancer invasion through dense extracellular matrices (ECMs) is mediated by matrix metalloproteinases (MMPs) which degrade the ECM thereby creating paths for migration. However, how this degradation influences the phenotype of cancer cells is not fully clear. Here we address this question by probing the function of MMPs in regulating biophysical properties of cancer cells relevant to invasion. We show that MMP catalytic activity regulates cell spreading, motility, contractility and cortical stiffness by stabilizing integrins at the membrane and activating focal adhesion kinase. Interestingly, cell rounding and cell softening on stiff gels induced by MMP inhibition is attenuated on MMP pre-conditioned surfaces. Together, our results suggest that MMP catalytic activity regulates invasiveness of cancer cells by modulating integrins.
format article
author Alakesh Das
Melissa Monteiro
Amlan Barai
Sandeep Kumar
Shamik Sen
author_facet Alakesh Das
Melissa Monteiro
Amlan Barai
Sandeep Kumar
Shamik Sen
author_sort Alakesh Das
title MMP proteolytic activity regulates cancer invasiveness by modulating integrins
title_short MMP proteolytic activity regulates cancer invasiveness by modulating integrins
title_full MMP proteolytic activity regulates cancer invasiveness by modulating integrins
title_fullStr MMP proteolytic activity regulates cancer invasiveness by modulating integrins
title_full_unstemmed MMP proteolytic activity regulates cancer invasiveness by modulating integrins
title_sort mmp proteolytic activity regulates cancer invasiveness by modulating integrins
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/d3662dc961f54566b67919e8a216311e
work_keys_str_mv AT alakeshdas mmpproteolyticactivityregulatescancerinvasivenessbymodulatingintegrins
AT melissamonteiro mmpproteolyticactivityregulatescancerinvasivenessbymodulatingintegrins
AT amlanbarai mmpproteolyticactivityregulatescancerinvasivenessbymodulatingintegrins
AT sandeepkumar mmpproteolyticactivityregulatescancerinvasivenessbymodulatingintegrins
AT shamiksen mmpproteolyticactivityregulatescancerinvasivenessbymodulatingintegrins
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