Entosis (from Greek ἐντός entos, "within" and -ωσις -osis, "disease") is the invasion of a living cell into another cell's cytoplasm. The process was discovered by Overholtzer, et al. as reported in Cell.
Entotic cells, also referred to as cell-in-cell structures, are triggered by loss of attachment to the extracellular matrix (ECM). This internalization of one cell by another is dependent on adherens junctions, and is driven by a Rho-dependent process, involving actin polymerization and myosin II activity in the internalized cell. Adherens junctions bind cells together by linking cadherin transmembrane protein complexes of adjacent cells to the cytoskeleton. When certain cell types are detached from the ECM and have lost adhesion, the compaction force between neighboring cells can cause them to push into their neighbors, forming the trademark cell-in-cell structures. Though cell-in-cell structures commonly refer to the interaction between two neighboring cells, entosis has been observed involving more than two cells. In the case of an entotic structure formed between three cells, the middle cell acts as both an internalizing and an outer host cell simultaneously.
Aneuploidy, a condition in which non-disjunction gives rise to gametes with an abnormal number of chromosomes, is one of the most prevalent phenotypes of human tumors. The underlying cause of aneuploidy remains highly debated; however, entosis is shown to perturb cytokinesis (cytoplasmic division) and trigger the formation of aneuploid cells. This would be in line with past research, as cell-in-cell structures have been widely observed in the focused study of many human tumors, including lung, breast, and endometrial stromal carcinomas.
A cell trapped by entosis is initially alive and can divide inside the cell that has enveloped it. On occasion, the entotic cell will be released by the host cell, but most internalized cells are eventually killed. Normal cells can kill themselves via apoptosis, involving the programmed engulfment and phagocytic ingestion of a cell by another. Entosis differs greatly from apoptosis in that the entotic process exhibits behavior closely resembling cellular invasion rather than cellular engulfment. Cancer cells adaptively avoid apoptosis, allowing them to live and multiply indefinitely, making it difficult to design drugs that effectively kill tumors. Therefore, entosis acts as a nonapoptotic cell death mechanism, and could possibly be a new way in which cancer cells can be killed.
- Janssen, Aniek; Rene H. Medema (1 March 2011). "Entosis: aneuploidy by invasion". Nature Cell Biology. 13: 199–201. doi:10.1038/ncb0311-199.
- Overholtzer, Michael; Arnaud A. Mailleux; Ghassan Mouneimne; Guillaume Normand; Stuart J. Schnitt; Randall W. King; Edmund S. Cibas; Joan S. Brugge (30 November 2007). "A Nonapoptotic Cell Death Process, Entosis, that Occurs by Cell-in-Cell Invasion". Cell. 131 (5): 966–979. doi:10.1016/j.cell.2007.10.040. PMID 18045538.
- Overholtzer, Michael. "An Interview with Michael Overholtzer". Memorial Sloan-Kettering Cancer Center. Retrieved 14 April 2012.
- Alberts, Bruce (2010). Essential Cell Biology, 3rd Ed. New York, NY: Garland Science, Taylor & Franis Group, LLC. pp. 662–663. ISBN 978-0-8153-4129-1.