Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis.

Animals Mice Cell Transformation, Neoplastic / genetics Inflammation / genetics Intracellular Signaling Peptides and Proteins / genetics Repressor Proteins / metabolism Tumor Microenvironment Tumor Suppressor Protein p53 / genetics MAP Kinase Kinase 4 / metabolism Transcription Factor AP-1 / metabolism
AP1/JNK CP: Cancer RAS iASPP inflammation-driven tumorigenesis p63 skin cancer target selective transcription

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
18 10 2022
Historique:
received: 26 12 2021
revised: 29 06 2022
accepted: 22 09 2022
entrez: 19 10 2022
pubmed: 20 10 2022
medline: 22 10 2022
Statut: ppublish

Résumé

Concurrent mutation of a RAS oncogene and the tumor suppressor p53 is common in tumorigenesis, and inflammation can promote RAS-driven tumorigenesis without the need to mutate p53. Here, we show, using a well-established mutant RAS and an inflammation-driven mouse skin tumor model, that loss of the p53 inhibitor iASPP facilitates tumorigenesis. Specifically, iASPP regulates expression of a subset of p63 and AP1 targets, including genes involved in skin differentiation and inflammation, suggesting that loss of iASPP in keratinocytes supports a tumor-promoting inflammatory microenvironment. Mechanistically, JNK-mediated phosphorylation regulates iASPP function and inhibits iASPP binding with AP1 components, such as JUND, via PXXP/SH3 domain-mediated interaction. Our results uncover a JNK-iASPP-AP1 regulatory axis that is crucial for tissue homeostasis. We show that iASPP is a tumor suppressor and an AP1 coregulator.

Identifiants

DOI: 10.1016/j.celrep.2022.111503 PMID: 36261000 PMC: PMC9597577
pubmed: 36261000
pii: S2211-1247(22)01353-5
doi: 10.1016/j.celrep.2022.111503
pmc: PMC9597577
pii:
doi:

Substances chimiques

Intracellular Signaling Peptides and Proteins 0
Repressor Proteins 0
Tumor Suppressor Protein p53 0
MAP Kinase Kinase 4 EC 2.7.12.2
Transcription Factor AP-1 0
Ppp1r13l protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

111503

Subventions

Organisme : Wellcome Trust
ID : 210641/Z/18/Z
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests X.L. is a scientific advisory board member of Oxford SimCell. T.M.C. is a founder, employee, and shareholder of a diagnostics company (Cleancard).

Références

Arthritis Res Ther. 2008;10(1):201
pubmed: 18226189
Hum Mol Genet. 2005 Mar 1;14(5):667-77
pubmed: 15661756
J Biol Chem. 1999 May 28;274(22):15662-70
pubmed: 10336463
J Invest Dermatol. 2019 Aug;139(8):1658-1671.e8
pubmed: 30710576
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Mol Cell Biol. 2004 Feb;24(3):1341-50
pubmed: 14729977
Hum Pathol. 2005 Feb;36(2):187-94
pubmed: 15754296
Mol Cell. 2001 Oct;8(4):781-94
pubmed: 11684014
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Cell. 2011 Feb 18;144(4):566-76
pubmed: 21335238
BMC Genet. 2012 Aug 28;13:76
pubmed: 22928477
Cell Death Discov. 2021 Jul 26;7(1):195
pubmed: 34312379
Bioinformatics. 2010 Apr 1;26(7):860-6
pubmed: 20147307
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
EMBO J. 2011 Sep 06;30(20):4261-73
pubmed: 21897369
Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14114-9
pubmed: 15375216
Mol Cell Biol. 2005 Jul;25(14):6077-89
pubmed: 15988020
BMC Genomics. 2014 Nov 29;15:1042
pubmed: 25433490
Nature. 2003 Feb 6;421(6923):639-43
pubmed: 12571598
Mol Syst Biol. 2011 Oct 11;7:539
pubmed: 21988835
Int J Mol Sci. 2019 Nov 17;20(22):
pubmed: 31744230
Structure. 2008 Feb;16(2):259-68
pubmed: 18275817
J Exp Med. 2008 Sep 29;205(10):2235-49
pubmed: 18809714
EMBO J. 1989 May;8(5):1433-9
pubmed: 2504580
Genome Biol. 2014;15(12):550
pubmed: 25516281
Methods. 2015 Apr;76:87-98
pubmed: 25524420
J Med Genet. 2002 Jun;39(6):377-81
pubmed: 12070241
Cell. 1987 Jun 19;49(6):729-39
pubmed: 3034432
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
J Cell Biochem. 2008 May 15;104(2):453-64
pubmed: 18044712
Genes Dev. 1999 Mar 1;13(5):607-19
pubmed: 10072388
J Biol Chem. 2007 Oct 19;282(42):31046-59
pubmed: 17681951
Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16645-50
pubmed: 21930934
Nat Genet. 2003 Feb;33(2):162-7
pubmed: 12524540
Cell. 1993 Apr 23;73(2):263-78
pubmed: 8477445
Biostatistics. 2017 Apr 1;18(2):275-294
pubmed: 27756721
J Biol Chem. 2015 Jul 24;290(30):18636-49
pubmed: 26018080
Int J Mol Med. 2014 Mar;33(3):695-702
pubmed: 24356997
Genome Biol. 2012 Mar 16;13(3):R16
pubmed: 22424423
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Cell. 1993 Sep 10;74(5):813-22
pubmed: 8374952
BMC Genomics. 2015 Aug 07;16:584
pubmed: 26251276
Bioinformatics. 2021 Mar 24;:
pubmed: 33760053
Cell Cycle. 2006 Dec;5(23):2805-11
pubmed: 17172858
Anim Genet. 2009 Feb;40(1):42-6
pubmed: 19016676
Genome Biol. 2008;9(9):R137
pubmed: 18798982
JCI Insight. 2020 Oct 15;5(20):
pubmed: 33055429
Elife. 2016 Mar 14;5:
pubmed: 27021569
EMBO Mol Med. 2017 Mar;9(3):319-336
pubmed: 28069640
Mol Med Rep. 2015 Aug;12(2):1653-8
pubmed: 25846425
Mol Cell Biol. 2011 Apr;31(7):1565-76
pubmed: 21282468
J Skin Cancer. 2013;2013:537028
pubmed: 23762562
Nucleic Acids Res. 2018 Jan 4;46(D1):D260-D266
pubmed: 29140473
Cancer Cell. 2013 May 13;23(5):618-33
pubmed: 23623661
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
J Cell Sci. 2000 May;113 ( Pt 10):1661-70
pubmed: 10769197
Nat Genet. 2006 Oct;38(10):1133-41
pubmed: 16964264
Sci Rep. 2019 Jun 27;9(1):9354
pubmed: 31249361
Oncotarget. 2015 Dec 15;6(40):42478-90
pubmed: 26646590
Nucleic Acids Res. 2019 Jan 8;47(D1):D766-D773
pubmed: 30357393
BMC Bioinformatics. 2010 May 11;11:237
pubmed: 20459804
Carcinogenesis. 1985 Feb;6(2):213-7
pubmed: 3156004
Anal Chem. 2012 Jun 5;84(11):5066-73
pubmed: 22530732
Neoplasma. 2011;58(3):205-10
pubmed: 21391736
Nat Protoc. 2008;3(5):799-810
pubmed: 18451788
Genes Dev. 1994 Feb 15;8(4):399-413
pubmed: 8125255
Nucleic Acids Res. 2019 Jan 8;47(D1):D330-D338
pubmed: 30395331
Front Immunol. 2018 Jun 11;9:1298
pubmed: 29942307
EMBO Rep. 2015 Jul;16(7):863-78
pubmed: 26034101
Mol Cell. 2000 Nov;6(5):1109-19
pubmed: 11106750
Nat Commun. 2019 Feb 15;10(1):771
pubmed: 30770806
Nature. 2005 Mar 17;434(7031):338-45
pubmed: 15735639
Cell. 2014 May 22;157(5):1130-45
pubmed: 24855949
Oncogene. 2004 Dec 2;23(56):9007-16
pubmed: 15489900
Nucleic Acids Res. 2010 Jul;38(Web Server issue):W695-9
pubmed: 20439314
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Oncogene. 2020 May;39(22):4436-4449
pubmed: 32350443
Protein Sci. 2007 Jan;16(1):30-42
pubmed: 17192587
JCI Insight. 2021 Jul 8;6(13):
pubmed: 34236045
J Invest Dermatol. 2005 Jan;124(1):212-20
pubmed: 15654976
Cell Death Differ. 2018 Jul;25(7):1289-1303
pubmed: 29352264
Methods Enzymol. 2015;562:109-33
pubmed: 26412649

Auteurs

Khatoun Al Moussawi (K)

Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK.

Kathryn Chung (K)

Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK.

Thomas M Carroll (TM)

Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK.

Christian Osterburg (C)

Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt, Germany.

Artem Smirnov (A)

Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK.

Rebecca Lotz (R)

Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt, Germany.

Paul Miller (P)

Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK.

Zinaida Dedeić (Z)

Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK.

Shan Zhong (S)

Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK.

Martin Oti (M)

Radboud University, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.

Evelyn N Kouwenhoven (EN)

Radboud University, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.

Ruth Asher (R)

Cellular Pathology, John Radcliffe Hospital, Oxford OX3 9DU, UK; Department of Histopathology, University Hospital Wales, Cardiff CF14 4XW, UK.

Robert Goldin (R)

Department of Pathology, Imperial College London, Faculty of Medicine at St Mary's, Norfolk Place, London W2 1PG, UK.

Michael Tellier (M)

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.

Shona Murphy (S)

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.

Huiqing Zhou (H)

Radboud University, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands; Radboud University Medical Centre, Department of Human Genetics, Radboud Institute for Molecular Life Sciences, 6500 Nijmegen, the Netherlands.

Volker Dötsch (V)

Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt, Germany.

Xin Lu (X)

Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: xin.lu@ludwig.ox.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Mutant Ras and inflammation-driven skin...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Mutant Ras and inflammation-driven skin...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › Transformation cellulaire néoplasique › Mutant Ras and inflammation-driven skin...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Mutant Ras and inflammation-driven skin...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Mutant Ras and inflammation-driven skin...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Mutant Ras and inflammation-driven skin...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Mutant Ras and inflammation-driven skin...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Protéine p53 suppresseur de tumeur › Mutant Ras and inflammation-driven skin...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-tyrosine kinases › Mitogen-Activated Protein Kinase Kinases › MAP Kinase Kinase 4 › Mutant Ras and inflammation-driven skin...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Facteur de transcription AP-1 › Mutant Ras and inflammation-driven skin...