Fig. 5: Intravasation and extravasation of cancer cells and mechanical resistance of CTCs via cytoskeletal modification and reorganization.
From: Roles of cytoskeleton in metastasis: from its mechanism to therapeutic strategies
a MenaINV, an isoform of Mena that increases during intravascular penetration, stabilizes actin filaments through PTP1B inhibition. Mena promotes the secretion of MMPs through interaction with microtubules. The increased expression of TGF-β1 upregulates vimentin to enhance the stability of the cytoskeleton. b CTCs express βIII-tubulin and Tau to form and stabilize microtentacles and reorganize the actin cytoskeleton into stress fibers. Vimentin increases the cell surface expression of integrin β1, which allows cell survival. c Microtentacles, formed by detyrosination of α-tubulin, facilitate the attachment of CTCs to endothelial cells. d The actomyosin contractility enhances the adhesion of CTCs to endothelial cells for extravasation. e During extravasation, invadopodia mature through integrin β1 and talin binding, increase MMP expression by CAMSAP2 and promote MMP secretion through the interaction of NEDD9 with vimentin, allowing cancer cells to pass through endothelial cells easily.
