-
Something wrong with this record ?
Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes
M. Krkoška, J. Svobodová, M. Kabátková, O. Zapletal, A. Hyršlová Vaculová, J. Nekvindová, J. Vondráček
Language English Country Ireland
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Cytochrome P-450 CYP1A1 biosynthesis genetics MeSH
- Enzyme Induction physiology MeSH
- HCT116 Cells MeSH
- Liver pathology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Colonic Neoplasms genetics pathology MeSH
- Cell Proliferation physiology MeSH
- E1A-Associated p300 Protein metabolism MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Hippo Signaling Pathway physiology MeSH
- Wnt Signaling Pathway physiology MeSH
- Signal Transduction physiology MeSH
- Cell Survival physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't 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.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc22003866
- 003
- CZ-PrNML
- 005
- 20220228091717.0
- 007
- ta
- 008
- 220113s2021 ie f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.tox.2021.152897 $2 doi
- 035 __
- $a (PubMed)34403729
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a ie
- 100 1_
- $a Krkoška, Martin $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
- 245 10
- $a Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes / $c M. Krkoška, J. Svobodová, M. Kabátková, O. Zapletal, A. Hyršlová Vaculová, J. Nekvindová, J. Vondráček
- 520 9_
- $a 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.
- 650 _2
- $a nádorové buněčné linie $7 D045744
- 650 _2
- $a proliferace buněk $x fyziologie $7 D049109
- 650 _2
- $a viabilita buněk $x fyziologie $7 D002470
- 650 _2
- $a nádory tračníku $x genetika $x patologie $7 D003110
- 650 _2
- $a cytochrom P-450 CYP1A1 $x biosyntéza $x genetika $7 D019363
- 650 _2
- $a protein p300 asociovaný s E1A $x metabolismus $7 D050881
- 650 _2
- $a enzymová indukce $x fyziologie $7 D004790
- 650 _2
- $a regulace genové exprese u nádorů $7 D015972
- 650 _2
- $a HCT116 buňky $7 D045325
- 650 _7
- $a signální dráha Hippo $x fyziologie $7 D000090683 $2 czmesh
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a játra $x patologie $7 D008099
- 650 _2
- $a signální transdukce $x fyziologie $7 D015398
- 650 _2
- $a signální dráha Wnt $x fyziologie $7 D060449
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Svobodová, Jana $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech Republic
- 700 1_
- $a Kabátková, Markéta $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech Republic
- 700 1_
- $a Zapletal, Ondřej $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech Republic
- 700 1_
- $a Hyršlová Vaculová, Alena $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech Republic
- 700 1_
- $a Nekvindová, Jana $u Institute of Clinical Biochemistry and Diagnostics, University Hospital Hradec Králové, Sokolská 581, 500 05 Hradec Králové, Czech Republic
- 700 1_
- $a Vondráček, Jan $u Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech Republic. Electronic address: vondracek@ibp.cz
- 773 0_
- $w MED00004533 $t Toxicology $x 1879-3185 $g Roč. 461, č. - (2021), s. 152897
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/34403729 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20220113 $b ABA008
- 991 __
- $a 20220228091715 $b ABA008
- 999 __
- $a ok $b bmc $g 1751358 $s 1155015
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2021 $b 461 $c - $d 152897 $e 20210814 $i 1879-3185 $m Toxicology $n Toxicology $x MED00004533
- LZP __
- $a Pubmed-20220113
