An Integrin-Linked Machinery of Cytoskeletal Regulation that Enables Experimental Tumor Initiation and Metastatic Colonization
Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels, en régulant le cytosquelette, l'intégrine favorise une transition épithélio-mésenchymateuse
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.
"Abundance of filopodium-like protrusions (FLPs) depends on their persistence periods "Integrin-actin linking proteins govern cofilin activity as well as FLP persistence "FLPs critically support both metastatic outgrowth and experimental tumor formation "Epithelial-mesenchymal transition (EMT) in carcinoma cells enhances FLP formation