Papel del receptor de dioxina en la regulación de la adhesión y migración celular en fibroblastosinteracciones con Integrina B1 y Caveolina 1

Résumé

The dioxin receptor (AhR) is a transcription factor with an important role in enviromental toxicology and physiology. Apart from that, cell adhesion and migration processes have shown to be crucial both in homeostasis and pathology. The present work focuses in the study of the role of the dioxin receptor in both cellular functions by using mouse fibroblast. This role is done through the control of integrin ?1 activation and the location and functionality of caveolin 1. In the first case, the regulation is driven by the combination of fibronectin expression control and the Cbp-Csk-Src pathway and has consequences in cellular shape, migration speed and contraction and matrix invasion capabilities. On the other hand, the caveolina 1 regulation by AhR involves changes in cellular location of the protein, as well as the sublocation in specific membrane domains (rafts) and is involved in cell re-orientation capability and endocytosis via caveolae. In this case, the control is not caused by phosphorylation state changes in Y14 residue of caveolina 1, but it does it in the case of intracellular cholesterol changes, driven by the dioxin receptor. Globaly, th results help us to understand the importance of AhR in cellular physiology as well as the pathways by AhR execute its functions.