SEMINAR: Federico Lucantoni

Speaker: Federico Lucantoni

Title: Pharmacological Activation of ROCK1 Signaling Triggers Entosis and Reveals Plastin 3 as Key Mediator

Abstract: Entosis is a recently characterized cell-in-cell program driven by homotypic cell invasion, in which one epithelial cell actively penetrates into another. This unique mechanism leads to the formation of cell-in-cell (CIC) structures and has drawn increasing attention for its potential roles in cancer biology.
The biological consequences of entosis are context-dependent. In some settings, it can suppress tumor growth through elimination of internalized cells, while in others, it may promote malignancy, for example by fostering genome instability or selecting for more aggressive clones. Notably, inner cells often remain viable for extended periods; they may persist quiescently, escape, or even divide within the host cell before escaping. However, the majority ultimately undergo a form of non-apoptotic cell death, known as entotic cell death, mediated by the host cell’s lysosomal machinery.
Despite its potential importance, entosis remains poorly understood, partly because it occurs in a small fraction of cells, making it challenging to study both in vitro and in vivo. While several conditions have been reported to induce entosis, these often lack specificity and trigger a range of cellular responses.
Importantly, the role of entosis in treatment resistance has not been fully elucidated. In our work, we applied genetic and chemical approaches to modulate a key molecular axis involved in this process. We found that ROCK1 activation significantly increases entosis frequency, and revealed novel targets that could participate in this process.