[3] In addition, events such as cellular atrophy and process retraction may also be mediated by dependence receptors, although this has not been as well documented as the induction of programmed cell death.
For any required stimulus, its withdrawal leads to a form of cellular suicide; that is, the cell plays an active role in its own demise.
This process is seen in developmental cell death, carcinogenesis (especially metastasis), neurodegeneration, and possibly non-lethal (sub-apoptotic) events such as neurite retraction and somal atrophy.
The signaling that mediates cell death induction upon ligand withdrawal is incompletely defined, but typically includes a required interaction with, and cleavage by, specific caspases.
Mutation of the caspase site(s) in the receptor, of which there is typically one or two, prevents the trophic ligand withdrawal-induced programmed cell death.
[citation needed] Research has highlighted the role of the dependence receptor UNC5D in the phenomenon of spontaneous regression of type IV-S neuroblastoma.