Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism

M. Diry (1) , C. Tomkiewicz (2) , C. Koehle (3) , Xavier Coumoul (2) , K. Walter Bock (3) , R. Barouki (2) , C. Transy (2)

1 IISVSP - IFR95 - Institut interdisciplinaire des sciences du vivant des Saints-Pères
2 T3S - UMR_S 1124 - Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire
3 Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen

Environmental chemicals such as dioxin adversely affect immune, neurological and reproductive functions and have been implicated in cancer development. However, the mechanisms responsible for dioxin toxicity are still poorly understood. Here, we show that dioxin and related pollutants trigger a marked morphological change in epithelial cells that remodel their cytoskeleton to increase interaction with extra cellular matrix while loosening cell-cell contacts. Furthermore, dioxin-treated cells show increased motility. These dioxin-mediated effects are mimicked by constitutive expression and activation of the intracellular dioxin receptor (aryl hydrocarbon receptor (AhR)). They correlate with activation of the Jun NH2-terminal kinase (JNK) and are reverted by treatment with a JNK inhibitor. Dioxin-induced effects occur 48 h post-treatment initiation, a time scale, which argues for a genomic effect of the AhR, linked to induction of target genes. This novel Ahr action on cell plasticity points to a role in cancer progression.

Domaines: Toxicologie

M. Diry, C. Tomkiewicz, C. Koehle, Xavier Coumoul, K. Walter Bock, et al.. Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism. Oncogene, 2006, 25 (40), pp.5570-5574. ⟨10.1038/sj.onc.1209553⟩. ⟨hal-02173983⟩