Graphical Abstract Highlights d MemBright allows for bright and specific staining of EVs d The zebrafish embryo allows tracking of tumor EVs at high spatiotemporal resolution d Circulating tumor EVs are mostly taken up by endothelial cells and patrolling macrophages d Zebrafish melanoma EVs favor metastatic outgrowth in zebrafish embryos

Highlights d Fast-moving cells in 3D matrix establish low membrane tension at the rear d Caveolae form in response to low membrane tension and recruit the GEF Ect2 d Ect2 activates RhoA to promote F-actin organization and rear retraction d Positive feedback between membrane tension and contractility reinforces retraction

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