Regulation of aquaporin-3 by the AHR pathway: critical for cell migration

AHR (aryl hydrocarbon receptor) is a transcription factor activated by innumerable foreign chemicals (“signals”). as well as by endogenous chemicals such as some in the lipid mediator (LM) second-messenger pathway. Down-regulation or ablation of AHR causes many irregularities in many critical life functions including birth defects, i.e. dysregulation of embryonic and fetal development. Regulation of cell migration and plasticity are key factors in embryonic development, and also for dissemination of metastatic cells during tumor progression. AHR also causes oxidative stress and tumor promotion through mechanisms not yet well understood.

Aquaporins are membrane channels that allow transmembrane fluxes of water and glycerol into cells in a variety of mammalian tissues. In the attached article, authors show that AQP3, which has been incriminated in cancer progression, is regulated by AHR. In mice, upon exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), ligand of AHR, expression of AQP3 is increased significantly in several tissues including liver. In cell culture, treatment of human hepatoma HepG2 cells with TCDD also increases the expression of AQP3 mRNA and protein.

These effects resulted from activation of AHR (shown by RNA interference, chromatin immunoprecipitation, and use of several AHR ligands). Immunofluorescence and real-time

analysis of cell migration demonstrated that knockdown of AQP3 mRNA using small interfering RNA impairs remodeling of cell shape and the triggering of cell migration, which is inducible by TCDD. This very interesting publication shows, for the first time, a link between AHR activation and aquaporin-3 induction, suspected to play a role during embryonic development and tumor metastasis. Tox_Sci_Cell_Migration_Aquaporin_2o16

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