An integrin-linked machinery of cytoskeletal regulation that enables experimental tumor initiation and metastatic colonization.
| Autor: | Shibue T; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; MIT Ludwig Center for Molecular Oncology, Cambridge, MA 02139, USA., Brooks MW, Weinberg RA |
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| Jazyk: | angličtina |
| Zdroj: | Cancer cell [Cancer Cell] 2013 Oct 14; Vol. 24 (4), pp. 481-98. Date of Electronic Publication: 2013 Sep 12. |
| DOI: | 10.1016/j.ccr.2013.08.012 |
| Abstrakt: | Recently extravasated metastatic cancer cells use the Rif/mDia2 actin-nucleating/polymerizing machinery in order to extend integrin β1-containing, filopodium-like protrusions (FLPs), which enable them to interact productively with the surrounding extracellular matrix; this process governs the initial proliferation of these cancer cells. Here, we identify the signaling pathway governing FLP lifetime, which involves integrin-linked kinase (ILK) and β-parvin, two integrin:actin-bridging proteins that block cofilin-mediated actin-filament severing. Notably, the combined actions of Rif/mDia2 and ILK/β-parvin/cofilin pathways on FLPs are required not only for metastatic outgrowth but also for primary tumor formation following experimental implantation. This provides one mechanistic explanation for how the epithelial-mesenchymal transition (EMT) program imparts tumor-initiating powers to carcinoma cells, since it enhances FLP formation through the activation of ILK/β-parvin/cofilin pathway. (Copyright © 2013 Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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