EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK
Regulation of microtubule dynamics by plus-end tracking proteins (+TIPs) plays an essential role in cancer cell migration. However, the role of +TIPs in cancer cell invasion has been poorly addressed. Invadopodia, actin-rich protrusions specialized in extracellular matrix degradation, are essential...
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MDPI AG
2021-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/388 |
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| author | Brice Chanez Kevin Ostacolo Ali Badache Sylvie Thuault |
| author_facet | Brice Chanez Kevin Ostacolo Ali Badache Sylvie Thuault |
| author_sort | Brice Chanez |
| collection | DOAJ |
| description | Regulation of microtubule dynamics by plus-end tracking proteins (+TIPs) plays an essential role in cancer cell migration. However, the role of +TIPs in cancer cell invasion has been poorly addressed. Invadopodia, actin-rich protrusions specialized in extracellular matrix degradation, are essential for cancer cell invasion and metastasis, the leading cause of death in breast cancer. We, therefore, investigated the role of the End Binding protein, EB1, a major hub of the +TIP network, in invadopodia functions. EB1 silencing increased matrix degradation by breast cancer cells. This was recapitulated by depletion of two additional +TIPs and EB1 partners, APC and ACF7, but not by the knockdown of other +TIPs, such as CLASP1/2 or CLIP170. The knockdown of Focal Adhesion Kinase (FAK) was previously proposed to similarly promote invadopodia formation as a consequence of a switch of the Src kinase from focal adhesions to invadopodia. Interestingly, EB1-, APC-, or ACF7-depleted cells had decreased expression/activation of FAK. Remarkably, overexpression of wild type FAK, but not of FAK mutated to prevent Src recruitment, prevented the increased degradative activity induced by EB1 depletion. Overall, we propose that EB1 restricts invadopodia formation through the control of FAK and, consequently, the spatial regulation of Src activity. |
| first_indexed | 2024-03-09T00:54:35Z |
| format | Article |
| id | doaj.art-7de176495ca54eeea4e9380648484a25 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T00:54:35Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7de176495ca54eeea4e9380648484a252023-12-11T16:57:51ZengMDPI AGCells2073-44092021-02-0110238810.3390/cells10020388EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAKBrice Chanez0Kevin Ostacolo1Ali Badache2Sylvie Thuault3Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM, Institut Paoli-Calmettes, Aix-Marseille University, CNRS, 13009 Marseille, FranceCentre de Recherche en Cancérologie de Marseille (CRCM), INSERM, Institut Paoli-Calmettes, Aix-Marseille University, CNRS, 13009 Marseille, FranceCentre de Recherche en Cancérologie de Marseille (CRCM), INSERM, Institut Paoli-Calmettes, Aix-Marseille University, CNRS, 13009 Marseille, FranceCentre de Recherche en Cancérologie de Marseille (CRCM), INSERM, Institut Paoli-Calmettes, Aix-Marseille University, CNRS, 13009 Marseille, FranceRegulation of microtubule dynamics by plus-end tracking proteins (+TIPs) plays an essential role in cancer cell migration. However, the role of +TIPs in cancer cell invasion has been poorly addressed. Invadopodia, actin-rich protrusions specialized in extracellular matrix degradation, are essential for cancer cell invasion and metastasis, the leading cause of death in breast cancer. We, therefore, investigated the role of the End Binding protein, EB1, a major hub of the +TIP network, in invadopodia functions. EB1 silencing increased matrix degradation by breast cancer cells. This was recapitulated by depletion of two additional +TIPs and EB1 partners, APC and ACF7, but not by the knockdown of other +TIPs, such as CLASP1/2 or CLIP170. The knockdown of Focal Adhesion Kinase (FAK) was previously proposed to similarly promote invadopodia formation as a consequence of a switch of the Src kinase from focal adhesions to invadopodia. Interestingly, EB1-, APC-, or ACF7-depleted cells had decreased expression/activation of FAK. Remarkably, overexpression of wild type FAK, but not of FAK mutated to prevent Src recruitment, prevented the increased degradative activity induced by EB1 depletion. Overall, we propose that EB1 restricts invadopodia formation through the control of FAK and, consequently, the spatial regulation of Src activity.https://www.mdpi.com/2073-4409/10/2/388breast cancerinvadopodiamicrotubules+TIPsFAKextracellular matrix |
| spellingShingle | Brice Chanez Kevin Ostacolo Ali Badache Sylvie Thuault EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK Cells breast cancer invadopodia microtubules +TIPs FAK extracellular matrix |
| title | EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK |
| title_full | EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK |
| title_fullStr | EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK |
| title_full_unstemmed | EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK |
| title_short | EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK |
| title_sort | eb1 restricts breast cancer cell invadopodia formation and matrix proteolysis via fak |
| topic | breast cancer invadopodia microtubules +TIPs FAK extracellular matrix |
| url | https://www.mdpi.com/2073-4409/10/2/388 |
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