It is well-known how TP53-mediated apoptosis helps to eliminate cancer cells. However, some advanced tumors usually present mutations in this pathway preventing cancer-cell death and leading to tumor progression.

Unexpectedly, MIT researchers lead by Dr. H. Robert Horvit, have recently published in Nature an alternative pathway known as cell extrusion, which may be also used to eliminate pre-cancerous or cancer cells and which seems to be initiated as well by TP53. Usually, when a cell is no longer required, it is “expulsed” from a layer without affecting the overall structure, for example in the intestine lining or in the lungs.

For the first time, MIT researchers have been able to correlate cell cycle, mostly CDK1, and the cell extrusion process. Unexpectedly, when a cell starts cell cycle and its DNA gets copied, but it cannot adequately complete cell cycle, it triggers the cell extrusion mechanism and gets sloughed off. It seems that these cells follow asymmetrical cell division because they have low levels of an enzyme called LRR-1, which is critical for DNA replication. When replication stress occurs, CDK1 is inactivated. Not surprisingly, CDK1 is also necessary for cell adhesion, thus it seems feasible that a cell is not following cell cycle progression adequately, it will be extruded out. Surprisingly, TP53 has been identify as well as an initialization mediator upon replication stress, but this mechanism mostly depends on the cell cycle machinery, making it more feasible to be targeted for potential novel cancer therapies.