Induction of entosis by epithelial cadherin expression

Qiang Sun, Edmund S. Cibas, Hongyan Huang, Louis Hodgson, Michael Overholtzer

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Cell engulfment typically targets dead or dying cells for clearance from metazoan tissues. However, recent evidence demonstrates that live cells can also be targeted and that engulfment can cause cell death. Entosis is one mechanism proposed to mediate the engulfment and killing of live tumor cells by their neighbors, an activity often referred to as cell cannibalism. Here we report that the expression of exogenous epithelial cadherin proteins (E- or P-cadherin) in human breast tumor cells lacking endogenous expression of epithelial cadherins induces entosis and inhibits transformed growth. Entosis induced by cadherin expression is associated with the polarized distribution of Rho and Rho-kinase (ROCK) activity within entotic cells, which is dependent on p190A RhoGAP activity. ROCK inhibition or downregulation of p190A RhoGAP expression reduces entosis and increases the transformed growth of epithelial cadherin-expressing tumor cells. These data define new cell systems for the study of entosis, and identify entosis as a mechanism of cell cannibalism that is induced by the establishment of epithelial adhesion and inhibits transformed growth.

Original languageEnglish (US)
Pages (from-to)1288-1298
Number of pages11
JournalCell Research
Volume24
Issue number11
DOIs
StatePublished - Nov 5 2014

    Fingerprint

Keywords

  • Rho GTPase
  • actomyosin
  • cadherin
  • entosis
  • p190A RhoGAP
  • tumor suppression

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Sun, Q., Cibas, E. S., Huang, H., Hodgson, L., & Overholtzer, M. (2014). Induction of entosis by epithelial cadherin expression. Cell Research, 24(11), 1288-1298. https://doi.org/10.1038/cr.2014.137