Interferon signaling promotes tolerance to chromosomal instability during metastatic evolution in renal cancer.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
25
04
2022
accepted:
18
05
2023
medline:
27
7
2023
pubmed:
27
6
2023
entrez:
26
6
2023
Statut:
ppublish
Résumé
Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR-Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate metastatic renal tumors. Disruption of 9p21 locus is an evolutionary driver to systemic disease through the rapid acquisition of complex karyotypes in cancer cells. Cross-species analysis revealed that recurrent patterns of copy number variations, including 21q loss and dysregulation of the interferon pathway, are major drivers of metastatic potential. In vitro and in vivo genomic engineering, leveraging loss-of-function studies, along with a model of partial trisomy of chromosome 21q, demonstrated a dosage-dependent effect of the interferon receptor genes cluster as an adaptive mechanism to deleterious chromosomal instability in metastatic progression. This work provides critical knowledge on drivers of renal cell carcinoma progression and defines the primary role of interferon signaling in constraining the propagation of aneuploid clones in cancer evolution.
Identifiants
pubmed: 37365326
doi: 10.1038/s43018-023-00584-1
pii: 10.1038/s43018-023-00584-1
pmc: PMC10368532
doi:
Banques de données
figshare
['10.6084/m9.figshare.21637199.v2']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
984-1000Subventions
Organisme : Medical Research Council
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s).
Références
Cell Rep. 2016 Mar 15;14(10):2476-89
pubmed: 26947078
Sci Transl Med. 2022 Jan 12;14(627):eabi4888
pubmed: 35020411
Cell Rep. 2018 Apr 3;23(1):313-326.e5
pubmed: 29617669
Cancer. 2021 Mar 15;127(6):840-849
pubmed: 33216356
Mamm Genome. 2011 Dec;22(11-12):685-91
pubmed: 21953412
Nat Biotechnol. 2019 Mar;37(3):224-226
pubmed: 30809026
Cell. 2018 Apr 5;173(2):321-337.e10
pubmed: 29625050
Ann Oncol. 2015 Jan;26(1):64-70
pubmed: 25319062
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Nat Protoc. 2020 Feb;15(2):266-315
pubmed: 31907453
Nucleic Acids Res. 2016 Sep 19;44(16):e131
pubmed: 27270079
Nat Genet. 2016 Oct;48(10):1119-30
pubmed: 27526321
Neuron. 2015 Mar 04;85(5):942-58
pubmed: 25741722
Nat Biotechnol. 2019 Mar;37(3):303-313
pubmed: 30833775
Genome Biol. 2009;10(3):R25
pubmed: 19261174
N Engl J Med. 2016 Jan 14;374(2):135-45
pubmed: 26536169
Genome Biol. 2011;12(4):R41
pubmed: 21527027
Nat Neurosci. 2010 Jan;13(1):133-40
pubmed: 20023653
Urol Oncol. 2021 Feb;39(2):134.e9-134.e16
pubmed: 33187886
Nat Commun. 2016 Oct 07;7:13131
pubmed: 27713405
Cancer Cell. 2018 Apr 9;33(4):676-689.e3
pubmed: 29622463
Clin Cancer Res. 2017 Nov 1;23(21):6686-6696
pubmed: 28710314
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Nature. 2017 Feb 16;542(7641):362-366
pubmed: 28178232
Eur Urol. 2016 Aug;70(2):348-57
pubmed: 26895810
Proc Natl Acad Sci U S A. 2019 Nov 26;116(48):24231-24241
pubmed: 31699819
Nature. 2022 Aug;608(7924):795-802
pubmed: 35978189
Cell. 2018 Sep 6;174(6):1347-1360
pubmed: 30193109
Nat Rev Genet. 2020 Jan;21(1):44-62
pubmed: 31548659
Nat Methods. 2017 Oct;14(10):979-982
pubmed: 28825705
Nat Genet. 2014 Aug;46(8):912-918
pubmed: 25017105
Cell Stem Cell. 2022 Jan 6;29(1):116-130.e7
pubmed: 34995493
PLoS One. 2014 May 06;9(5):e96801
pubmed: 24802416
Nat Rev Clin Oncol. 2019 Oct;16(10):621-633
pubmed: 30992569
Nature. 2018 Jan 25;553(7689):467-472
pubmed: 29342134
Cell Rep. 2019 Feb 5;26(6):1518-1532.e9
pubmed: 30726735
Nat Genet. 2020 Jan;52(1):74-83
pubmed: 31907488
World J Urol. 2016 Aug;34(8):1081-6
pubmed: 26847337
Cancer Cell. 2020 May 11;37(5):720-734.e13
pubmed: 32359397
PLoS Comput Biol. 2016 Apr 21;12(4):e1004873
pubmed: 27100738
Nat Genet. 2011 May;43(5):491-8
pubmed: 21478889
Nat Rev Urol. 2015 Dec;12(12):706-12
pubmed: 26526752
Nat Struct Mol Biol. 2009 Dec;16(12):1244-51
pubmed: 19935685
J Urol. 2017 Sep;198(3):530-537
pubmed: 28411072
Mol Imaging. 2003 Oct;2(4):297-302
pubmed: 14717328
Nature. 2011 Sep 14;477(7364):326-9
pubmed: 21921916
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Lancet. 2000 Jan 15;355(9199):165-9
pubmed: 10675114
Cell. 2018 Apr 19;173(3):581-594.e12
pubmed: 29656895
Nat Commun. 2017 Jun 08;8:15770
pubmed: 28593993
Clin Cancer Res. 2018 Jul 15;24(14):3299-3308
pubmed: 29618619
Nat Med. 2020 Jun;26(6):909-918
pubmed: 32472114
Cell. 2022 Feb 3;185(3):563-575.e11
pubmed: 35120664
Bioinformatics. 2009 Nov 1;25(21):2865-71
pubmed: 19561018
Genome Med. 2021 Jan 6;13(1):2
pubmed: 33407829
Nat Med. 2020 Nov;26(11):1733-1741
pubmed: 32895571
Nat Methods. 2018 Aug;15(8):591-594
pubmed: 30013048
Nature. 2013 Aug 22;500(7463):415-21
pubmed: 23945592
Elife. 2018 Sep 04;7:
pubmed: 30178746
Genome Res. 2012 Mar;22(3):568-76
pubmed: 22300766
Nature. 2018 Feb 1;554(7690):62-68
pubmed: 29364867
Cell. 2016 Oct 6;167(2):397-404.e9
pubmed: 27667683
N Engl J Med. 2016 Sep 1;375(9):819-29
pubmed: 27433843
Genes Dev. 2002 Nov 15;16(22):2958-70
pubmed: 12435636
Nat Commun. 2021 Feb 5;12(1):808
pubmed: 33547292
J Mol Diagn. 2015 May;17(3):251-64
pubmed: 25801821
Genes Dev. 2015 Jul 15;29(14):1576-85
pubmed: 26178787