Entosis: the core mechanism and crosstalk with other cell death programs

Abstract

Cell death pathways play critical roles in organism development and homeostasis as well as in the pathogenesis of various diseases. While studies over the last decade have elucidated numerous different forms of cell death that can eliminate cells in various contexts, how certain mechanisms impact physiology is still not well understood. Moreover, recent studies have shown that multiple forms cell death can occur in a cell population, with different forms of death eliminating individual cells. Here, we aim to describe the known molecular mechanisms of entosis, a non-apoptotic cell engulfment process, and discuss signaling mechanisms that control its induction as well as its possible crosstalk with other cell death mechanisms.

Fig. 1. The core entosis mechanism and its regulatory pathways.

Top: Conditions and treatments that lead to the induction of entosis through regulation of the core mechanism. Bottom: The core mechanism of entotic cell-in-cell structure formation consists of cell‒cell adhesion and actomyosin contraction, depicted in bold. Between neighboring cells with adherens junctions formed through cadherin molecules, the differential mechanical deformability imparted by RhoA–ROCK signaling-mediated actomyosin contraction serves as the driving force for the internalization of the engulfed, or “loser”, cell into the engulfing, or “winner”, cell. Inhibitors blocking each component of the core mechanism are depicted in red. The core entosis mechanism can be regulated by various pathways induced by oncogenes, tumor suppressor genes, or stress signaling.