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Cancer Cell. 2013 Oct 14;24(4):481-98. doi: 10.1016/j.ccr.2013.08.012. Epub 2013 Sep 12.

An integrin-linked machinery of cytoskeletal regulation that enables experimental tumor initiation and metastatic colonization.

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Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; MIT Ludwig Center for Molecular Oncology, Cambridge, MA 02139, USA.

Erratum in

  • Cancer Cell. 2013 Dec 9;24(6):806-8.


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.

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