Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain.
Cell Adh Migr. 2010 Apr-Jun;4(2):172-5. doi: 10.4161/cam.4.2.10387. Epub 2010 Apr 21.
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.
二恶英受体 (AhR) 可能是研究得最透彻的外源性受体，因为它在介导高毒性环境污染物的有害作用方面发挥着重要作用。尽管 AhR 依赖性毒性是一个主要的环境问题，但最近有令人信服的证据揭示了 AhR 在细胞生理学和组织稳态中的新的、显著的内源性功能。除了在细胞增殖和分化中的作用外，AhR 还参与细胞黏附和迁移的控制，这在发育和癌症等疾病状态中都是非常重要的任务。有趣的是，AhR 对细胞迁移的影响具有细胞类型特异性，因为它可以维持或减缓细胞的迁移能力。在这里，我将对我们最近的报告进行评论，该报告表明 AhR 是成纤维细胞迁移的正向调节剂。除了对这种间充质细胞的表型进行描述外，我们研究的最重要的单一发现是，AhR 使用细胞骨架调节剂和致癌基因 Vav3 通过小 Rho GTPases 发出信号，最终导致细胞黏附和迁移的生理控制。这些数据表明 AhR 活性对于维持控制正常细胞功能的信号通路是必需的，并提出了一个问题，即 AhR 是否在发育过程中的细胞迁移以及肿瘤转移等病理条件下发挥作用。
