Abstract
Dissemination of transformed cells is a key process in metastasis. Despite its importance, how transformed cells disseminate from an intact tissue and enter the circulation is poorly understood. Here, we use a fully developed tissue, Drosophila midgut, and describe the morphologically distinct steps and the cellular events occurring over the course of RasV12-transformed cell dissemination. Notably, RasV12-transformed cells formed the Actin- and Cortactin-rich invasive protrusions that were important for breaching the extracellular matrix (ECM) and visceral muscle. Furthermore, we uncovered the essential roles of the mechanosensory channel Piezo in orchestrating dissemination of RasV12-transformed cells. Collectively, our study establishes an in vivo model for studying how transformed cells migrate out from a complex tissue and provides unique insights into the roles of Piezo in invasive cell behavior.
Highlights
Dissemination of transformed cells is a key process in metastasis
Observing the cell dissemination process in a native context allows us to describe actin- and cortactin-rich invasive protrusions that are associated with degradation of the extracellular matrix (ECM) and the visceral muscle (VM) layer in Drosophila and discover the mechanosensitive channel Piezo as a key player of cell dissemination in vivo
We found that cortactin overexpression in RasV12, piezo RNA inference (RNAi) cells restored Mmp[1] levels (Fig. 6d), the formation of large blebs/protrusions across VM (Fig. 6e), and the VM damage (Fig. 6f) to the extent caused by RasV12 cells
Summary
Dissemination of transformed cells is a key process in metastasis. Despite its importance, how transformed cells disseminate from an intact tissue and enter the circulation is poorly understood. The same study elucidated that sustained intestinal infection with pathogenic bacteria could enhance dissemination of RasV12-expressing hindgut cells via activation of Imd innate immune signaling[14] These tumor models have allowed the identification of several genetic and environmental factors underlying metastatic phenotypes[12,13,14,16,17], it still remains obscure how these transformed cells disseminate from the primary tumor site into the hemocoel to initiate metastasis. Observing the cell dissemination process in a native context allows us to describe actin- and cortactin-rich invasive protrusions that are associated with degradation of the ECM and the visceral muscle (VM) layer in Drosophila and discover the mechanosensitive channel Piezo as a key player of cell dissemination in vivo
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