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MERCIER, L.

Publications and source records attributed to MERCIER, L..

2 recordsLinked to original sources

Tks5 interactome reveals ER-associated machinery translation in invadosomes.

The ability to progress and invade through the extracellular matrix is a characteristic shared by both normal and cancer cells through the formation of structures called invadosomes gathering invadopodia and podosomes. These invadosomes are plastic and dynamic structures that can adopt different organizations depending on the cell types and the environment such as rosettes, dots or linear invadosomes. In this study, we used the specific invadosome marker Tks5 (SH3PXD2A), to identify common features in these different organizations. Tks5 immunoprecipitation coupled with mass spectrometry analysis allowed us to identify common proteins in these different models. We identified elements of the translation machinery, in particular the EIF4B protein, but also endoplasmic reticulum (ER) proteins as part of the invadosome structure. Providing new data on invadosome molecular composition through Tks5 interactome, we identified that ER-associated translation machinery is recruited to invadosome and involved in their formation, persistence and function in all types of invadosomes. SummaryInvadosomes are invasive F-actin structures exhibiting different organizations that degrade the extracellular matrix. The study uses their universal marker, Tks5, to provide new data about invadosome molecular composition and reveal the role of ER-associated translation machinery in invadosome formation and function.

cancer biology↗

Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells

Tumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified prometastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis revealed that blood flow modulated several signaling pathways in endothelial cells. More specifically, we observed that VEGFR signaling was significantly enhanced. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented with sunitinib, a pan-inhibitor of VEGFR signaling. Embryos treated with sunitinib displayed reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression. Highlights- Flow profiles that are permissive for metastasis stimulate the VEGFR pathway - Flow-dependent VEGFR signaling favors extravasation of CTCs through endothelial remodeling - Inhibition of VEGFR signaling suppresses early flow-driven endothelial response

cancer biology↗