Dependence receptors: life or death choices.

Dependence receptors: life or death choices. Bull Cancer. 2013 Nov 18; Authors: Delcros JG, Mehlen P Abstract Whereas the classic dogma postulates that transmembrane receptors remain inactive at the plasma membrane unless bound by their specific ligand, it was suggested that some receptors may actually be active not only in the presence of their ligand, but also in their absence. In this latter case, the signaling downstream of these unbound receptors leads to apoptosis. These receptors were consequently named dependence receptors, as their cell expression renders the survival of the cell dependent on the presence in the cell environment of its respective ligand. This dual function - positive in the presence of ligand, negative in the absence of ligand - is hypothesized to lead these receptors to have key roles both during embryonic development and in the regulation of tumorigenesis. In the context of cancer, the hypothesis is that these receptors are tumor suppressors that would limit tumor progression by inducing apoptosis of tumor cells outside of settings of ligand accessibility/availability. This was recently formally demonstrated for the prototypical dependence receptors that bind netrin-1- i.e., DCC and UNC5H. Because expression of DCC and UNC5H is a constraint for tumor progression, their expression is often lost in many aggressive cancers. However, a loss of dependence receptors is not always the selective advantage used by tumor c...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research