Cell Death by Entosis: Triggers, Molecular Mechanisms and Clinical Significance

Abstract

Entosis-a homotypic insertion of one cell into another, resulting in a death of the invading cell-has been described in many reports, but crucial aspects of its molecular mechanisms and clinical significance still remain controversial. While actomyosin contractility of the invading cell is very well established as a driving force in the initial phase, and autophagy induced in the outer cell is determined as the main mechanism of degradation of the inner cell, many details remain unresolved. The multitude of triggering factors and crisscrossing molecular pathways described in entosis regulation make interpretations difficult. The question of the physiological role of entosis also remains unanswered. In this review, we summarize the knowledge of molecular mechanisms and clinical data concerning entosis accumulated so far, highlighting both coherent explanations and controversies.

Keywords: actomyosin contractility; autophagy; cell-in-cell; entosis; programed cell death.

Figure 1

Entosis from initiation to completion; various triggers induce cytoskeletal changes, resulting in the formation of cell-in-cell structure. Both internal and external cells are prone to aneuploidy. Viable internal cells may still escape or divide, but the majority are destroyed by autophagy and lysosome fusion.