title: Induction of entosis by epithelial cadherin expression.
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.
authors.affiliation: 1] Laboratory of Cell Engineering, Institute of Biotechnology, Beijing 100071, China [2] Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Edmund S
authors.initials: ES
authors.lastname: Cibas
authors.affiliation: Department of Oncology, Beijing Shijitan Hospital of Capital Medical University, 10 TIEYI Road, Beijing 100038, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Anatomy and Structural Biology and Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Hodgson
authors.affiliation: 1] Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA [2] BCMB Allied Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Overholtzer
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D057691:Entosis; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D009218:Myosins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D059008:Time-Lapse Imaging; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C074560:ARHGAP35 protein, human; D015820:Cadherins; D020662:Guanine Nucleotide Exchange Factors; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000205:Actomyosin; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; D009218:Myosins; D020742:rhoA GTP-Binding Protein