A Nonapoptotic Cell Death Process, Entosis, that Occurs by Cell-in-Cell Invasion

Michael Overholtzer, Arnaud A. Mailleux, Ghassan Mouneimne, Guillaume Normand, Stuart J. Schnitt, Randall W. King, Edmund S. Cibas, Joan S. Brugge

Research output: Contribution to journalArticle

355 Scopus citations

Abstract

Epithelial cells require attachment to extracellular matrix (ECM) to suppress an apoptotic cell death program termed anoikis. Here we describe a nonapoptotic cell death program in matrix-detached cells that is initiated by a previously unrecognized and unusual process involving the invasion of one cell into another, leading to a transient state in which a live cell is contained within a neighboring host cell. Live internalized cells are either degraded by lysosomal enzymes or released. We term this cell internalization process entosis and present evidence for entosis as a mechanism underlying the commonly observed "cell-in-cell" cytological feature in human cancers. Further we propose that entosis is driven by compaction force associated with adherens junction formation in the absence of integrin engagement and may represent an intrinsic tumor suppression mechanism for cells that are detached from ECM.

Original languageEnglish (US)
Pages (from-to)966-979
Number of pages14
JournalCell
Volume131
Issue number5
DOIs
StatePublished - Nov 30 2007
Externally publishedYes

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Keywords

  • CELLBIO
  • HUMDISEASE

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Overholtzer, M., Mailleux, A. A., Mouneimne, G., Normand, G., Schnitt, S. J., King, R. W., Cibas, E. S., & Brugge, J. S. (2007). A Nonapoptotic Cell Death Process, Entosis, that Occurs by Cell-in-Cell Invasion. Cell, 131(5), 966-979. https://doi.org/10.1016/j.cell.2007.10.040