Volume 24, No 11, Nov 2014
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 24 Issue 11, November 2014: 1288-1298
ORIGINAL ARTICLES
Induction of entosis by epithelial cadherin expression
Qiang Sun1,2, Edmund S Cibas3, Hongyan Huang4, Louis Hodgson5 and Michael Overholtzer2,6
1Laboratory of Cell Engineering, Institute of Biotechnology, Beijing 100071, China
2Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
3Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
4Department of Oncology, Beijing Shijitan Hospital of Capital Medical University, 10 TIEYI Road, Beijing 100038, China
5Department of Anatomy and Structural Biology and Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA
6BCMB Allied Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA
Correspondence: Michael Overholtzer, Tel: +1 212-639-6536; Fax: +1 212-794-4342
E-mail: overhom1@mskcc.org; Qiang Sun, Tel: 86-10-66948820 (sunqiang1975@126.com)
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.
10.1038/cr.2014.137
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