A non-genetic route to aneuploidy in human cancers

Abstract

Aneploidy is frequently observed in cancer. It is now shown that aneploidy can arise by entosis, the process of live cell internalisation by a neighbouring cell. The internalised cell can interfere with host cell division and disrupt the formation of the contractile actin ring resulting in cytokinesis defects and aneuploidy. 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.

Cite this article

Krajcovic, M., Johnson, N., Sun, Q. et al. A non-genetic route to aneuploidy in human cancers. Nat Cell Biol 13, 324–330 (2011). https://doi.org/10.1038/ncb2174

View full text

>> Full Text:   A non-genetic route to aneuploidy in human cancers