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@article{962162,
author = {Procházková, Jiřina and Kabátková, Markéta and Bryja, Vítězslav and Umannová, Lenka and Bernatík, Ondřej and Kozubík, Alois and Machala, Miroslav and Vondráček, Jan},
article_number = {2},
doi = {http://dx.doi.org/10.1093/toxsci/kfr129},
keywords = {Wnt signaling; dioxin; intercellular junctions; contact inhibition; liver progenitor cells; differentiation},
language = {eng},
issn = {1096-6080},
journal = {Toxicological sciences},
title = {The interplay of the aryl hydrocarbon receptor and beta-catenin alters both AhR-dependent transcription and Wnt/beta catenin signaling in liver progenitors.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21602191},
volume = {122},
year = {2011}
}
TY - JOUR
ID - 962162
AU - Procházková, Jiřina - Kabátková, Markéta - Bryja, Vítězslav - Umannová, Lenka - Bernatík, Ondřej - Kozubík, Alois - Machala, Miroslav - Vondráček, Jan
PY - 2011
TI - The interplay of the aryl hydrocarbon receptor and beta-catenin alters both AhR-dependent transcription and Wnt/beta catenin signaling in liver progenitors.
JF - Toxicological sciences
VL - 122
IS - 2
SP - 349-360
EP - 349-360
SN - 10966080
KW - Wnt signaling
KW - dioxin
KW - intercellular junctions
KW - contact inhibition
KW - liver progenitor cells
KW - differentiation
UR - http://www.ncbi.nlm.nih.gov/pubmed/21602191
L2 - http://www.ncbi.nlm.nih.gov/pubmed/21602191
N2 - beta-catenin is a key integrator of cadherin-mediated cell-cell adhesion and transcriptional regulation through the Wnt/beta-catenin pathway, which plays an important role in liver biology. Using a model of contact-inhibited liver progenitor cells, we examined the interactions of Wnt/beta-catenin signaling with the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, which mediates the toxicity of dioxin-like compounds, including their effects on development and hepatocarcinogenesis. We found that AhR and Wnt/beta-catenin cooperated in the induction of AhR transcriptional targets, such as Cyp1a1 and Cyp1b1. However, simultaneously, the activation of AhR led to a decrease of dephosphorylated active beta-catenin pool, as well as to hypophosphorylation of Dishevelled, participating in regulation of Wnt signaling. A sustained AhR activation by its model ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), led to a downregulation of a number of Wnt/beta-catenin pathway target genes. TCDD also induced a switch in cytokeratin expression, where downregulation of cytokeratins 14 and 19 was accompanied with an increased cytokeratin 8 expression. Together with a downregulation of additional markers associated with stem-like phenotype, this indicated that the AhR activation interfered with differentiation of liver progenitors.
ER -
PROCHÁZKOVÁ, Jiřina, Markéta KABÁTKOVÁ, Vítězslav BRYJA, Lenka UMANNOVÁ, Ondřej BERNATÍK, Alois KOZUBÍK, Miroslav MACHALA and Jan VONDRÁČEK. The interplay of the aryl hydrocarbon receptor and beta-catenin alters both AhR-dependent transcription and Wnt/beta catenin signaling in liver progenitors. \textit{Toxicological sciences}. 2011, vol.~122, No~2, p.~349-360. ISSN~1096-6080. Available from: https://dx.doi.org/10.1093/toxsci/kfr129.
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