Patterning of individual cellular behavior in collective invasion

Collective invasion is one of the most important factors accounting for the aggressiveness of solid tumors. Such behavior depends on interactions between tumor cells and between tumor and its surrounding miroenvironment, including stroma cells and extracellular matrix (ECM), which to a certain extent, can be observed in normal cells. Previously we have shown that epithelial cells can use cell-ECM-cell interaction to develop long-range (> 600 microns) invasive patterns. Here, using artificial wounding assay, we show that normal epithelial cells can develop two coexisting, orthogonal migration patterns at the tissue boundary, leading to a periodic patterning of invasion. Such patterning depends on microtubule dynamic instability and results in ROCK activation and YAP1 nuclear translocation, a process to induce epithelial-mesenchymal transition (EMT). Surprisingly, we found that both overexpression and knockdown of an EMT marker, vimentin, can enhance collective invasion, suggesting that the role of vimentin in EMT might be context dependent and needs to be revisited. Citation Format: Chin-Lin Guo, Emilio Sanchez, Eileen Fong. Patterning of individual cellular behavior in collective invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5165.