[Dependence receptors: links between apoptosis, nervous system development and control of tumorigenesis].
The dependence receptor notion was based on the observation that the effects of a number of receptors that function in both nervous system development and tumorigenesis (especially metastasis) cannot be explained simply by a positive effect of signal transduction induced by ligand binding. Receptors such as the common neurotrophin receptor p75NTR, the androgen receptor (AR), DCC (deleted in colorectal cancer), and RET (rearranged during transfection) demonstrate effects that are more adequately explained when these are considered to be dependence receptors. These receptors show two distinct forms of signal transduction depending on their respective ligand availability: in the presence of their ligands, they transduce a signal for either proliferation or differentiation; however, they are not inactive in the absence of their ligands, but rather induce an active signal for cell death. Such receptors thus create a cellular state of dependence on their ligands, the loss of ligand availability inducing cell suicide or enhancing the likelihood of cellular suicide. This new concept is reviewed here enlightening the molecular mechanisms of these receptors and their potential relevance in vivo in the development of the nervous system and in the control of tumorigenesis.
Mehlen
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Apoptose/différenciation, équipe labellisée <<La Ligue>>, Centre de génétique moléculaire et cellulaire CNRS UMR 5534, Université Lyon-1, 43, bd du 11-Novembre-1918, 69622 Villeurbanne.
Bredesen
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D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D000075389:DCC Receptor; D029721:Drosophila Proteins; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D051379:Mice; D009420:Nervous System / Q000196:embryology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D020800:Receptor, Nerve Growth Factor / Q000502:physiology*; D011944:Receptors, Androgen / Q000502:physiology*; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; C501910:Dcc protein, mouse; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D011944:Receptors, Androgen; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse; D020169:Caspases