Entosis: Cellular Canabalism
There might be more to cell death besides apoptosis and necrosis. In a paper that sounded a bit fishy to me, Michael Overholtzer, Joan Brugge and coworkers1 introduce “Entosis”: A non-apoptotic cell death process, that occurs by cell-in-cell invasion.
As Eileen White2 described:
Upon examination of mammary epithelial cell lines in suspension, Overholtzer et al. noticed the presence of cells within other cells. Further investigation of this phenomenon revealed that detachment of mammary epithelial cells from the ECM initiates a new pathway of nonapoptotic cell death called entosis in which one cell invades into another.
How in the world did these researchers notice that the rounded-up cells were actually inside of other cells, as opposed to merely on top of one another in the microscope’s field of view? I know that I might have easily overlooked such an observation, which tells me that Overholtzer et al. were really paying close attention.
Even so, how did they confirm that the dying cells were actually internalized, and not merely autophagy or apoptosis? Time-lapse microscopy was a good start, especially with the z-series image reconstruction, giving the researchers a 3-dimensional view. Next they tested caspase-3 activity in relation to the timescale of cell engulfment observations, as well as known activators and inhibitors of the apoptotic program. No effect.
But influencing signaling factors involved in regulating cell shape and movement did have an effect on the observed cell engulfment, especially Actin, Myosin II, Rho, and ROCK activity. Detachment from the extracellular matrix (ECM) was required for entosis also. And cadherins appeared to moderate internalization via adherens junctions. So this newly described process isn’t autophagy either.
And the result for most of the engulfed cells? Death by lysosome.
- Overholtzer M, Mailleux AA, Mouneimne G, Normand G, Schnitt SJ, King RW, Cibas ES, Brugge JS. A Nonapoptotic Cell Death Process, Entosis, that Occurs by Cell-in-Cell Invasion. Cell. 30 Nov. 2007; 131(5):966-979. DOI:10.1016/j.cell.2007.10.040
- White E. Entosis: It’s a Cell-Eat-Cell World. Cell. 30 Nov. 2007; 131(5):840-842. DOI:10.1016/j.cell.2007.11.015
molecular biology
