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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Nature Portfolio
2017
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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) |
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DOAJ |
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Medicine R Science Q |
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Medicine R Science Q Alakesh Das Melissa Monteiro Amlan Barai Sandeep Kumar Shamik Sen MMP proteolytic activity regulates cancer invasiveness by modulating integrins |
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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 |
_version_ |
1718388924285452288 |