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EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK

Abstract : 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.
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https://hal-amu.archives-ouvertes.fr/hal-03174359
Contributor : Ali Badache Connect in order to contact the contributor
Submitted on : Tuesday, March 30, 2021 - 2:43:46 PM
Last modification on : Tuesday, October 19, 2021 - 10:59:17 PM

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Brice Chanez, Kevin Ostacolo, Ali Badache, Sylvie Thuault. EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK. Cells, MDPI, 2021, 10 (2), pp.388. ⟨10.3390/cells10020388⟩. ⟨hal-03174359⟩

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