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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-14340-w |
| _version_ | 1818344037272256512 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T16:40:06Z |
| format | Article |
| id | doaj.art-d3662dc961f54566b67919e8a216311e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T16:40:06Z |
| publishDate | 2017-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d3662dc961f54566b67919e8a216311e2022-12-21T23:38:19ZengNature PortfolioScientific Reports2045-23222017-10-017111310.1038/s41598-017-14340-wMMP proteolytic activity regulates cancer invasiveness by modulating integrinsAlakesh Das0Melissa Monteiro1Amlan Barai2Sandeep Kumar3Shamik Sen4Department of Biosciences & Bioengineering, IIT BombayDepartment of Biosciences & Bioengineering, IIT BombayDepartment of Biosciences & Bioengineering, IIT BombayDepartment of Biosciences & Bioengineering, IIT BombayDepartment of Biosciences & Bioengineering, IIT BombayAbstract 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.https://doi.org/10.1038/s41598-017-14340-w |
| spellingShingle | Alakesh Das Melissa Monteiro Amlan Barai Sandeep Kumar Shamik Sen MMP proteolytic activity regulates cancer invasiveness by modulating integrins Scientific Reports |
| title | 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_short | MMP proteolytic activity regulates cancer invasiveness by modulating integrins |
| title_sort | mmp proteolytic activity regulates cancer invasiveness by modulating integrins |
| url | https://doi.org/10.1038/s41598-017-14340-w |
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