A remarkable new target gene for the dioxin receptor: The Vav3 proto-oncogene links AhR to adhesion and migration.
The dioxin receptor (AhR) is possibly the best characterized xenobiotic receptor because of its essential role in mediating the harmful effects of highly toxic environmental pollutants. Despite the fact that AhR-dependent toxicity is a major environmental concern, compelling evidence has recently been produced unveiling novel and remarkable endogenous functions of AhR in cell physiology and tissue homeostasis. Adding to its role in cell proliferation and differentiation, AhR is also involved in the control of cell adhesion and migration, both highly relevant tasks in development and in disease states such as cancer. Interestingly, the effect of AhR on cell migration is cell-type specific because it can sustain or slow down cell motility. Here, I will comment on our recent report showing that AhR is a positive regulator of fibroblast cells migration. Besides characterizing the phenotype of such mesenchymal cells, the most important single finding of our study is that AhR uses the cytoskeleton regulator and oncogen Vav3 to signal through small Rho GTPases, ultimately leading to the physiological control of cell adhesion and migration. These data reveal that AhR activity is required to maintain signaling pathways governing normal cell function and open the question of whether AhR plays a role in cell migration during development and in pathological conditions such as tumor metastasis.
Fernandez-Salguero
Pedro M
PM
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain. pmfersal@unex.es
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D000090063:Proto-Oncogene Mas; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051567:Proto-Oncogene Proteins c-vav; D018336:Receptors, Aryl Hydrocarbon