What triggers entosis?

Entosis is triggered by the loss of attachment to the extracellular matrix (ECM). Entosis involves the formation of adherens junctions and the generation of actomyosin contractility, which stimulates one cell to actively drive itself into an adjacent cell. This causes the inner cell to be digested and killed by the outer cell. Entosis can also occur in circumstances where cells lose their attachment to neighboring cells. In addition to a loss of attachment to the ECM or adjacent cells, entosis may be triggered by factors such as mitosis, hypoxia, glucose starvation, and acidic pH. Glucose starvation promotes competition between cancer cells as they respond to cellular stress. Glucose starvation induces entosis by activating the kinase AMPK within the internal cells and the internal cells ultimately become neutralized by the external cells. Mitotic entosis occurs in some human cancer cells, as adherent, wild-type cells may act as entotic hosts. This suggests that normal epithelial cells may engulf atypical dividing cells. Hypoxia can activate Rho GTPases, which cause changes in the actin cytoskeleton. Acidic pH may alter the function of cell-cell adhesion molecules such as E-cadherin and B1 integrin. It is suggested acidosis-induced changes in adhesion molecules may weaken intracellular adhesion, and thus promote the engulfment of one cell by another.