The SWI/SNF complex member SMARCB1 supports lineage fidelity in kidney cancer.
Cancer
Cellular physiology
Human genetics
Medical microbiology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
18 Aug 2023
18 Aug 2023
Historique:
received:
28
03
2023
revised:
22
05
2023
accepted:
07
07
2023
medline:
9
8
2023
pubmed:
9
8
2023
entrez:
9
8
2023
Statut:
epublish
Résumé
Lineage switching can induce therapy resistance in cancer. Yet, how lineage fidelity is maintained and how it can be lost remain poorly understood. Here, we have used CRISPR-Cas9-based genetic screening to demonstrate that loss of SMARCB1, a member of the SWI/SNF chromatin remodeling complex, can confer an advantage to clear cell renal cell carcinoma (ccRCC) cells upon inhibition of the renal lineage factor PAX8. Lineage factor inhibition-resistant ccRCC cells formed tumors with morphological features, but not molecular markers, of neuroendocrine differentiation. SMARCB1 inactivation led to large-scale loss of kidney-specific epigenetic programs and restoration of proliferative capacity through the adoption of new dependencies on factors that represent rare essential genes across different cancers. We further developed an analytical approach to systematically characterize lineage fidelity using large-scale CRISPR-Cas9 data. An understanding of the rules that govern lineage switching could aid the development of more durable lineage factor-targeted and other cancer therapies.
Identifiants
pubmed: 37554444
doi: 10.1016/j.isci.2023.107360
pii: S2589-0042(23)01437-2
pmc: PMC10405256
doi:
Types de publication
Journal Article
Langues
eng
Pagination
107360Subventions
Organisme : Medical Research Council
ID : MC_UU_12022/7
Pays : United Kingdom
Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
Nat Commun. 2018 Dec 3;9(1):5139
pubmed: 30510198
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Science. 2019 Mar 15;363(6432):1222-1226
pubmed: 30872526
Nature. 1998 Jul 9;394(6689):203-6
pubmed: 9671307
PLoS Genet. 2007 Aug;3(8):e136
pubmed: 17708682
Nat Med. 2021 May;27(5):802-805
pubmed: 33888901
Mol Syst Biol. 2017 Jan 9;13(1):905
pubmed: 28069687
Nature. 2019 May;569(7757):503-508
pubmed: 31068700
Nat Commun. 2021 Mar 12;12(1):1661
pubmed: 33712601
Curr Top Dev Biol. 2014;110:317-38
pubmed: 25248481
Nat Commun. 2019 Jun 27;10(1):2832
pubmed: 31249312
Nature. 2022 Jun;606(7916):999-1006
pubmed: 35676472
Cell. 2018 Nov 15;175(5):1272-1288.e20
pubmed: 30343899
Nat Cell Biol. 2018 Dec;20(12):1410-1420
pubmed: 30397315
Sci Rep. 2018 Aug 13;8(1):12063
pubmed: 30104738
Nucleic Acids Res. 2016 Jul 8;44(W1):W160-5
pubmed: 27079975
Nat Rev Drug Discov. 2022 Mar;21(3):181-200
pubmed: 35042991
Cancer Discov. 2022 Oct 5;12(10):2308-2329
pubmed: 35758895
Nat Commun. 2017 Mar 06;8:14648
pubmed: 28262751
Nature. 2012 Oct 18;490(7420):412-6
pubmed: 23051752
Genome Biol. 2014;15(12):550
pubmed: 25516281
Science. 2021 Jul 16;373(6552):306-315
pubmed: 34437148
Nat Commun. 2019 Aug 20;10(1):3739
pubmed: 31431624
Nat Genet. 2017 Nov;49(11):1613-1623
pubmed: 28945250
Cancer Cell. 2008 Dec 9;14(6):447-57
pubmed: 19061836
CA Cancer J Clin. 2021 May;71(3):209-249
pubmed: 33538338
Clin Cancer Res. 2020 Feb 15;26(4):793-803
pubmed: 31727677
Immunity. 2002 Dec;17(6):703-12
pubmed: 12479817
EMBO J. 2019 Oct 1;38(19):e101233
pubmed: 31414712
Cell Rep. 2013 Dec 26;5(6):1704-13
pubmed: 24332856
Nat Genet. 2020 Feb;52(2):187-197
pubmed: 31913353
Cell. 2018 Apr 19;173(3):595-610.e11
pubmed: 29656894
PLoS One. 2013 Jun 17;8(6):e66558
pubmed: 23799116
Cancer Discov. 2018 Aug;8(8):935-943
pubmed: 29899062
Nat Rev Clin Oncol. 2020 Jun;17(6):360-371
pubmed: 32152485
Nat Methods. 2013 Dec;10(12):1213-8
pubmed: 24097267
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Nature. 2013 Jul 4;499(7456):43-9
pubmed: 23792563
Cancer Discov. 2018 May;8(5):582-599
pubmed: 29510988
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Cancer Cell. 2018 May 14;33(5):890-904.e5
pubmed: 29657129
Nat Rev Cancer. 2010 Mar;10(3):205-12
pubmed: 20147902
Nat Med. 2016 Mar;22(3):298-305
pubmed: 26855148
Sci Rep. 2019 Jun 27;9(1):9354
pubmed: 31249361
Cell. 2022 Feb 3;185(3):563-575.e11
pubmed: 35120664
Annu Rev Pathol. 2007;2:145-73
pubmed: 18039096
Am J Surg Pathol. 2013 Oct;37(10):1490-504
pubmed: 24025520
Nat Med. 2013 Jan;19(1):50-6
pubmed: 23223005
Mod Pathol. 2009 Sep;22(9):1218-27
pubmed: 19525927
Science. 2014 Jan 3;343(6166):80-4
pubmed: 24336569
Annu Rev Immunol. 2001;19:623-55
pubmed: 11244049
Cancer Discov. 2018 Jul;8(7):850-865
pubmed: 29875134
Nat Genet. 2017 Dec;49(12):1779-1784
pubmed: 29083409
Nat Cell Biol. 2016 Dec;18(12):1269-1280
pubmed: 27820600
Cell. 2017 Jul 27;170(3):577-592.e10
pubmed: 28753431
Cancer Cell. 2020 Apr 13;37(4):584-598.e11
pubmed: 32220301
Biochim Biophys Acta. 2015 Feb;1852(2):365-78
pubmed: 24807060
Nat Chem Biol. 2012 Jan 29;8(3):277-84
pubmed: 22286128
Nat Commun. 2015 Mar 11;6:6377
pubmed: 25758528
Cell. 2017 Jul 27;170(3):564-576.e16
pubmed: 28753430
Cancer Cell. 2019 Jul 8;36(1):17-34.e7
pubmed: 31287989
Exp Cell Res. 2020 Mar 15;388(2):111845
pubmed: 31945318
Nat Commun. 2020 Nov 3;11(1):5549
pubmed: 33144576
Cell. 2012 Mar 2;148(5):1015-28
pubmed: 22385965
Diagn Pathol. 2010 May 12;5:28
pubmed: 20462442
Nat Genet. 2013 Jun;45(6):592-601
pubmed: 23644491
Nat Struct Mol Biol. 2016 Apr;23(4):349-57
pubmed: 26926434
Cell. 2018 Feb 8;172(4):650-665
pubmed: 29425488
Genes Dev. 2002 Nov 15;16(22):2958-70
pubmed: 12435636
Nat Genet. 2020 Feb;52(2):198-207
pubmed: 31932695
Nat Commun. 2021 Feb 5;12(1):808
pubmed: 33547292