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Cell cycle S-phase arrest drives cell extrusion

View ORCID ProfileVivek K. Dwivedi, View ORCID ProfileCarlos Pardo-Pastor, Rita Droste, Daniel P. Denning, View ORCID ProfileJody Rosenblatt, H. Robert Horvitz
doi: https://doi.org/10.1101/839845
Vivek K. Dwivedi
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Carlos Pardo-Pastor
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Rita Droste
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Daniel P. Denning
Novartis Institutes for BioMedical Research, Cambridge, MA 02139Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Jody Rosenblatt
Randall Division of Cell and Molecular Biophysics, King’s College London, London SE1 1UL, UK
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H. Robert Horvitz
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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  • For correspondence: horvitz@mit.edu
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SUMMARY

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 13, 2019.
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Cell cycle S-phase arrest drives cell extrusion
Vivek K. Dwivedi, Carlos Pardo-Pastor, Rita Droste, Daniel P. Denning, Jody Rosenblatt, H. Robert Horvitz
bioRxiv 839845; doi: https://doi.org/10.1101/839845
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Cell cycle S-phase arrest drives cell extrusion
Vivek K. Dwivedi, Carlos Pardo-Pastor, Rita Droste, Daniel P. Denning, Jody Rosenblatt, H. Robert Horvitz
bioRxiv 839845; doi: https://doi.org/10.1101/839845

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