title: A non-genetic route to aneuploidy in human cancers.
abstract: Aneuploidy is common in human tumours and is often indicative of aggressive disease. Aneuploidy can result from cytokinesis failure, which produces binucleate cells that generate aneuploid offspring with subsequent divisions. In cancers, disruption of cytokinesis is known to result from genetic perturbations to mitotic pathways or checkpoints. Here we describe a non-genetic mechanism of cytokinesis failure that occurs as a direct result of cell-in-cell formation by entosis. Live cells internalized by entosis, which can persist through the cell cycle of host cells, disrupt formation of the contractile ring during host cell division. As a result, cytokinesis frequently fails, generating binucleate cells that produce aneuploid cell lineages. In human breast tumours, multinucleation is associated with cell-in-cell structures. These data define a previously unknown mechanism of cytokinesis failure and aneuploid cell formation that operates in human cancers.
authors.affiliation: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Matej
authors.initials: M
authors.lastname: Krajcovic
authors.forename: Nicole B
authors.initials: NB
authors.lastname: Johnson
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.forename: Guillaume
authors.initials: G
authors.lastname: Normand
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hoover
authors.forename: Evelyn
authors.initials: E
authors.lastname: Yao
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Richardson
authors.forename: Randall W
authors.initials: RW
authors.lastname: King
authors.forename: Edmund S
authors.initials: ES
authors.lastname: Cibas
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Schnitt
authors.forename: Joan S
authors.initials: JS
authors.lastname: Brugge
authors.forename: Michael
authors.initials: M
authors.lastname: Overholtzer
mesh_terms: D000782:Aneuploidy; D002460:Cell Line; D045744:Cell Line, Tumor; D019070:Cell Lineage; D048749:Cytokinesis; D057691:Entosis; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008856:Microscopy, Fluorescence / Q000379:methods; D008938:Mitosis; D008954:Models, Biological; D008957:Models, Genetic; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D049452:Green Fluorescent Proteins