The phosphoinositide-binding protein ZF21 regulates ECM degradation by invadopodia.
During the process of tumor invasion, cells require footholds on extracellular matrices (ECM) that are created by forming focal adhesions (FAs) using integrins. On the other hand, cells must degrade the ECM barrier using extracellular proteases including MMPs in the direction of cell movement. Degra...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3561396?pdf=render |
| _version_ | 1818265989353046016 |
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| author | Daisuke Hoshino Makoto Nagano Anri Saitoh Naohiko Koshikawa Takashi Suzuki Motoharu Seiki |
| author_facet | Daisuke Hoshino Makoto Nagano Anri Saitoh Naohiko Koshikawa Takashi Suzuki Motoharu Seiki |
| author_sort | Daisuke Hoshino |
| collection | DOAJ |
| description | During the process of tumor invasion, cells require footholds on extracellular matrices (ECM) that are created by forming focal adhesions (FAs) using integrins. On the other hand, cells must degrade the ECM barrier using extracellular proteases including MMPs in the direction of cell movement. Degradation occurs at the leading edges or invadopodia of cells, which are enriched in proteases and adhesion molecules. Recently, we showed that the phosphoinositide-binding protein ZF21 regulates FA disassembly. ZF21 increased cell migration by promoting the turnover of FAs. In addition, ZF21 promotes experimental tumor metastasis to lung in mice and its depletion suppresses it. However, it is not known whether ZF21 regulates cancer cell invasion in addition to its activity on FAs. In this study, we demonstrate that ZF21 also regulates invasion of tumor cells, whereas it does not affect the overall production of MMP-2, MMP-9, and MT1-MMP by the cells. Also, we observe that the ECM-degrading activity specifically at the invadopodia is severely abrogated. In the ZF21 depleted cells MT1-MMP cannot accumulate to the invadopodia and thereby cannot contribute to the ECM degradation. Thus, this study demonstrates that ZF21 is a key player regulating multiple aspects of cancer cell migration and invasion. Possible mechanisms regulating ECM degradation at the invadopodia are discussed. |
| first_indexed | 2024-12-12T19:59:34Z |
| format | Article |
| id | doaj.art-cf3c758c99fe4d27936e8d85126883f8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T19:59:34Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cf3c758c99fe4d27936e8d85126883f82022-12-22T00:13:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5082510.1371/journal.pone.0050825The phosphoinositide-binding protein ZF21 regulates ECM degradation by invadopodia.Daisuke HoshinoMakoto NaganoAnri SaitohNaohiko KoshikawaTakashi SuzukiMotoharu SeikiDuring the process of tumor invasion, cells require footholds on extracellular matrices (ECM) that are created by forming focal adhesions (FAs) using integrins. On the other hand, cells must degrade the ECM barrier using extracellular proteases including MMPs in the direction of cell movement. Degradation occurs at the leading edges or invadopodia of cells, which are enriched in proteases and adhesion molecules. Recently, we showed that the phosphoinositide-binding protein ZF21 regulates FA disassembly. ZF21 increased cell migration by promoting the turnover of FAs. In addition, ZF21 promotes experimental tumor metastasis to lung in mice and its depletion suppresses it. However, it is not known whether ZF21 regulates cancer cell invasion in addition to its activity on FAs. In this study, we demonstrate that ZF21 also regulates invasion of tumor cells, whereas it does not affect the overall production of MMP-2, MMP-9, and MT1-MMP by the cells. Also, we observe that the ECM-degrading activity specifically at the invadopodia is severely abrogated. In the ZF21 depleted cells MT1-MMP cannot accumulate to the invadopodia and thereby cannot contribute to the ECM degradation. Thus, this study demonstrates that ZF21 is a key player regulating multiple aspects of cancer cell migration and invasion. Possible mechanisms regulating ECM degradation at the invadopodia are discussed.http://europepmc.org/articles/PMC3561396?pdf=render |
| spellingShingle | Daisuke Hoshino Makoto Nagano Anri Saitoh Naohiko Koshikawa Takashi Suzuki Motoharu Seiki The phosphoinositide-binding protein ZF21 regulates ECM degradation by invadopodia. PLoS ONE |
| title | The phosphoinositide-binding protein ZF21 regulates ECM degradation by invadopodia. |
| title_full | The phosphoinositide-binding protein ZF21 regulates ECM degradation by invadopodia. |
| title_fullStr | The phosphoinositide-binding protein ZF21 regulates ECM degradation by invadopodia. |
| title_full_unstemmed | The phosphoinositide-binding protein ZF21 regulates ECM degradation by invadopodia. |
| title_short | The phosphoinositide-binding protein ZF21 regulates ECM degradation by invadopodia. |
| title_sort | phosphoinositide binding protein zf21 regulates ecm degradation by invadopodia |
| url | http://europepmc.org/articles/PMC3561396?pdf=render |
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