EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK
Open Access
- 13 February 2021
- Vol. 10 (2), 388
- https://doi.org/10.3390/cells10020388
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.Keywords
This publication has 56 references indexed in Scilit:
- Targeting and transport: How microtubules control focal adhesion dynamicsThe Journal of cell biology, 2012
- Hic-5 promotes invadopodia formation and invasion during TGF-β–induced epithelial–mesenchymal transitionThe Journal of cell biology, 2012
- ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cellsProceedings of the National Academy of Sciences of the United States of America, 2010
- Actin, microtubules, and vimentin intermediate filaments cooperate for elongation of invadopodiaThe Journal of cell biology, 2010
- Laminin‐332–β1 integrin interactions negatively regulate invadopodiaJournal of Cellular Physiology, 2009
- Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cellsThe Journal of cell biology, 2009
- FAK alters invadopodia and focal adhesion composition and dynamics to regulate breast cancer invasionThe Journal of cell biology, 2009
- GSK3β phosphorylation modulates CLASP–microtubule association and lamella microtubule attachmentThe Journal of cell biology, 2009
- ACF7 Regulates Cytoskeletal-Focal Adhesion Dynamics and Migration and Has ATPase ActivityCell, 2008
- Paxillin Phosphorylation Controls Invadopodia/Podosomes Spatiotemporal OrganizationMolecular Biology of the Cell, 2008