Editors' ChoiceCell Biology

Distributing apoptosis protects epithelia

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Science Signaling  29 Jun 2021:
Vol. 14, Issue 689, eabk1364
DOI: 10.1126/scisignal.abk1364

EGFR signaling protects the integrity of epithelia by ensuring that apoptosis events are limited in both space and time.

Apoptotic cells are eliminated from epithelia in a process that couples the extrusion of individual dying cells with the formation of new junctions between the healthy cells that are left behind. Apoptotic cells also stimulate the survival and proliferation of neighboring cells. Together, these mechanisms ensure that epithelia retain barrier function despite high rates of cell turnover. Two studies report that epidermal growth factor receptor (EGFR) signaling maintains the integrity of fly and human epithelia by preventing the simultaneous apoptosis of neighboring cells. Valon et al. found that naturally occurring apoptosis and extrusion events in the pupal fly notum were limited to single cells, pairs of cells, or linear arrangements of cells. Inducing simultaneous apoptosis in clusters of three or more neighboring cells compromised tissue integrity. Transient activation of extracellular signal–regulated kinase (ERK) downstream of EGFR in cells neighboring an extruded cell protected the neighbors from caspase activation and apoptosis for about one hour after extrusion. In a related study, Gagliardi et al. demonstrated that apoptotic human mammary epithelial cells stimulated Akt and ERK activation in their neighbors in a manner that depended on EGFR and the matrix metalloproteases that release EGFR ligands. This protected the neighbors from apoptosis for a few hours and was required for the maintenance of epithelial integrity after starvation or treatment with cytotoxic drugs. Thus, EGFR signaling protects epithelia by ensuring that apoptotic events are distributed in both time and space.

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