PT  - JOURNAL ARTICLE
AU  - Vivek K. Dwivedi
AU  - Carlos Pardo-Pastor
AU  - Rita Droste
AU  - Daniel P. Denning
AU  - Jody Rosenblatt
AU  - H. Robert Horvitz
TI  - Cell cycle S-phase arrest drives cell extrusion
AID  - 10.1101/839845
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 839845
4099  - http://biorxiv.org/content/early/2019/11/13/839845.short
4100  - http://biorxiv.org/content/early/2019/11/13/839845.full
AB  - Cell extrusion is a process of cell elimination in which a cell is squeezed out from its tissue of origin. Extrusion occurs in organisms as diverse as sponges, nematodes, insects, fish and mammals. Defective extrusion is linked to many epithelial disorders, including cancer. Despite broad occurrence, cell-intrinsic triggers of extrusion conserved across phyla are generally unknown. We combined genome-wide genetic screens with live-imaging studies of C. elegans embryos and mammalian epithelial cultures and found that S-phase arrest induced extrusion in both. Cells extruded from C. elegans embryos exhibited S-phase arrest, and RNAi treatments that specifically prevent S-phase entry or arrest blocked cell extrusion. Pharmacological induction of S-phase arrest was sufficient to promote cell extrusion from a canine epithelial monolayer. Thus, we have discovered an evolutionarily conserved cell-cycle-dependent trigger of cell extrusion. We suggest that S-phase-arrest induced cell extrusion plays a key role in physiology and disease.