A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion.
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.
Overholtzer
Michael
M
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Mailleux
Arnaud A
AA
Mouneimne
Ghassan
G
Normand
Guillaume
G
Schnitt
Stuart J
SJ
King
Randall W
RW
Cibas
Edmund S
ES
Brugge
Joan S
JS
D000199:Actins / Q000502:physiology; D022005:Adherens Junctions / Q000502:physiology; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D001943:Breast Neoplasms / Q000473:pathology; D015820:Cadherins / Q000502:physiology; D002277:Carcinoma / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D024462:Myosin Type II / Q000502:physiology; D014407:Tumor Cells, Cultured; D020741:rho GTP-Binding Proteins / Q000502:physiology; D054460:rho-Associated Kinases / Q000502:physiology
D000199:Actins; D015820:Cadherins; D054460:rho-Associated Kinases; D024462:Myosin Type II; D020741:rho GTP-Binding Proteins