Entosis Is Induced by Glucose Starvation

Publication date: 5 July 2017
Source:Cell Reports, Volume 20, Issue 1
Author(s): Jens C. Hamann, Alexandra Surcel, Ruoyao Chen, Carolyn Teragawa, John G. Albeck, Douglas N. Robinson, Michael Overholtzer
Entosis is a mechanism of cell death that involves neighbor cell ingestion. This process occurs in cancers and promotes a form of cell competition, where winner cells engulf and kill losers. Entosis is driven by a mechanical differential that allows softer cells to eliminate stiffer cells. While this process can be induced by matrix detachment, whether other stressors can activate entosis is unknown. Here, we find that entosis is induced in adherent cells by glucose withdrawal. Glucose withdrawal leads to a bimodal distribution of cells based on their deformability, where stiffer cells appear in a manner requiring the energy-sensing AMP-activated protein kinase (AMPK). We show that loser cells with high levels of AMPK activity are eliminated by winners through entosis, which supports winner cell proliferation under nutrient-deprived conditions. Our findings demonstrate that entosis serves as a cellular response to metabolic stress that enables nutrient recovery through neighbor cell ingestion.

Graphical abstract

Teaser

Entosis has been shown to occur in human cancers and promotes cell competition. Hamann et al. now show that nutrient deprivation, in the form of glucose withdrawal, induces entosis to support the outgrowth of winner cells that feed off of losers.


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