Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes
Jazyk angličtina Země Irsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
34403729
DOI
10.1016/j.tox.2021.152897
PII: S0300-483X(21)00220-1
Knihovny.cz E-zdroje
- Klíčová slova
- AhR, CYP1 enzymes, Cancer cells, Cell proliferation, p300, β-Catenin signaling,
- MeSH
- cytochrom P-450 CYP1A1 biosyntéza genetika MeSH
- enzymová indukce fyziologie MeSH
- HCT116 buňky MeSH
- játra patologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory tračníku genetika patologie MeSH
- proliferace buněk fyziologie MeSH
- protein p300 asociovaný s E1A metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- signální dráha Hippo fyziologie MeSH
- signální dráha Wnt fyziologie MeSH
- signální transdukce fyziologie MeSH
- viabilita buněk fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CYP1A1 protein, human MeSH Prohlížeč
- cytochrom P-450 CYP1A1 MeSH
- EP300 protein, human MeSH Prohlížeč
- protein p300 asociovaný s E1A MeSH
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 siRNA-mediated 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.
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