Epigenetically heterogeneous tumor cells direct collective invasion through filopodia-driven fibronectin micropatterning
Emily R. Summerbell, Janna K. Mouw, Joshua S. K. Bell, Christina M. Knippler, Brian Pedro, Jamie L. Arnst, Tala O. Khatib, Rachel Commander, Benjamin G. Barwick, Jessica Konen, Bhakti Dwivedi, Sandra Seby, Jeanne Kowalski, Paula M. Vertino, Adam I. Marcus
Abstract
expression in leader cells. Using live-cell imaging, we found that MYO10 drives filopodial persistence necessary for micropatterning extracellular fibronectin into linear tracks at the edge of 3D collective invasion exclusively in leaders. Our data fit a model where epigenetic heterogeneity and JAG1 signaling jointly drive collective cancer invasion through MYO10 up-regulation in epigenetically permissive leader cells, which induces filopodia dynamics necessary for linearized fibronectin micropatterning.