First Author | Shibue T | Year | 2013 |
Journal | Cancer Cell | Volume | 24 |
Issue | 4 | Pages | 481-98 |
PubMed ID | 24035453 | Mgi Jnum | J:203427 |
Mgi Id | MGI:5527016 | Doi | 10.1016/j.ccr.2013.08.012 |
Citation | Shibue T, et al. (2013) An integrin-linked machinery of cytoskeletal regulation that enables experimental tumor initiation and metastatic colonization. Cancer Cell 24(4):481-98 |
abstractText | Recently extravasated metastatic cancer cells use the Rif/mDia2 actin-nucleating/polymerizing machinery in order to extend integrin beta1-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 beta-parvin, two integrin:actin-bridging proteins that block cofilin-mediated actin-filament severing. Notably, the combined actions of Rif/mDia2 and ILK/beta-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/beta-parvin/cofilin pathway. |