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@article{1790917,
author = {Krkoška, Martin and Svobodová, Jana and Kabátková, Markéta and Zapletal, Ondřej and Hyršlová Vaculová, Alena and Nekvindová, Jana and Vondráček, Jan},
article_number = {September},
doi = {http://dx.doi.org/10.1016/j.tox.2021.152897},
keywords = {Cell proliferation; AhR; p300; CYP1 enzymes; β-Catenin signaling; Cancer cells},
language = {eng},
issn = {0300-483X},
journal = {Toxicology},
title = {Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes},
url = {https://doi.org/10.1016/j.tox.2021.152897},
volume = {461},
year = {2021}
}
TY - JOUR
ID - 1790917
AU - Krkoška, Martin - Svobodová, Jana - Kabátková, Markéta - Zapletal, Ondřej - Hyršlová Vaculová, Alena - Nekvindová, Jana - Vondráček, Jan
PY - 2021
TI - Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes
JF - Toxicology
VL - 461
IS - September
SP - "152897"
EP - "152897"
PB - Elsevier Ireland Ltd
SN - 0300483X
KW - Cell proliferation
KW - AhR
KW - p300
KW - CYP1 enzymes
KW - β-Catenin signaling
KW - Cancer cells
UR - https://doi.org/10.1016/j.tox.2021.152897
N2 - Cytochrome P450 family 1 (CYP1) enzymes contribute both to metabolism of xenobiotics and to the control of endogenous levels of ligands of the aryl hydrocarbon receptor (AhR). Their activities, similar to other CYPs, can be altered in tumor tissues. Here, we examined a possible role of proliferative/survival pathways signaling, which is often deregulated in tumor cells, and possible links with p300 histone acetyltransferase (a transcriptional co-activator) in the control of CYP1 expression, focusing particularly on CYP1A1. Using cell models derived from human liver, we observed that the induction of CYP1A1 expression, as well as other CYP1 enzymes, was reduced in exponentially growing cells, as compared with their non-dividing counterparts. The siRNAmediated inhibition of proliferation/pro-survival signaling pathway effectors (such as β-catenin and/or Hippo pathway effectors YAP/TAZ) increased the AhR ligand-induced CYP1A1 mRNA levels in liver HepaRG cells, and/ or in colon carcinoma HCT-116 cells. The activation of proliferative Wnt/β-catenin signaling in HCT-116 cells reduced both the induction of CYP1 enzymes and the binding of p300 to the promoter of CYP1A1 or CYP1B1 genes. These results seem to indicate that aberrant proliferative signaling in tumor cells could suppress induction of CYP1A1 (or other CYP1 enzymes) via competition for p300 binding. This mechanism could be involved in modulation of the metabolism of both endogenous and exogenous substrates of CYP1A1 (and other CYP1 enzymes), with possible further consequences for alterations of the AhR signaling in tumor cells, or additional functional roles of CYP1 enzymes.
ER -
KRKOŠKA, Martin, Jana SVOBODOVÁ, Markéta KABÁTKOVÁ, Ondřej ZAPLETAL, Alena HYRŠLOVÁ VACULOVÁ, Jana NEKVINDOVÁ a Jan VONDRÁČEK. Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes. \textit{Toxicology}. Elsevier Ireland Ltd, 2021, roč.~461, September, s.~''152897'', 10 s. ISSN~0300-483X. Dostupné z: https://dx.doi.org/10.1016/j.tox.2021.152897.
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