Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
09 09 2022
09 09 2022
Historique:
pubmed:
19
8
2022
medline:
14
9
2022
entrez:
18
8
2022
Statut:
ppublish
Résumé
Drug resistance in cancer is often linked to changes in tumor cell state or lineage, but the molecular mechanisms driving this plasticity remain unclear. Using murine organoid and genetically engineered mouse models, we investigated the causes of lineage plasticity in prostate cancer and its relationship to antiandrogen resistance. We found that plasticity initiates in an epithelial population defined by mixed luminal-basal phenotype and that it depends on increased Janus kinase (JAK) and fibroblast growth factor receptor (FGFR) activity. Organoid cultures from patients with castration-resistant disease harboring mixed-lineage cells reproduce the dependency observed in mice by up-regulating luminal gene expression upon JAK and FGFR inhibitor treatment. Single-cell analysis confirms the presence of mixed-lineage cells with increased JAK/STAT (signal transducer and activator of transcription) and FGFR signaling in a subset of patients with metastatic disease, with implications for stratifying patients for clinical trials.
Identifiants
pubmed: 35981096
doi: 10.1126/science.abn0478
pmc: PMC9653178
mid: NIHMS1840456
doi:
Substances chimiques
Androgen Antagonists
0
Janus Kinase Inhibitors
0
STAT Transcription Factors
0
EGFR protein, mouse
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Janus Kinases
EC 2.7.10.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1180-1191Subventions
Organisme : NCI NIH HHS
ID : P50 CA092629
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA155169
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224079
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209975
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA193837
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA259161
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA265768
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA208100
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Références
Nature. 2019 May;569(7756):361-367
pubmed: 30959515
Cell. 2018 Aug 23;174(5):1293-1308.e36
pubmed: 29961579
Nat Rev Cancer. 2020 Apr;20(4):247-257
pubmed: 32094544
Genes Dev. 2018 Jul 1;32(13-14):915-928
pubmed: 29945888
Commun Biol. 2020 Dec 16;3(1):778
pubmed: 33328604
J Vis Exp. 2019 Oct 24;(152):
pubmed: 31710046
J Mol Diagn. 2015 May;17(3):251-64
pubmed: 25801821
Nat Med. 2021 Mar;27(3):546-559
pubmed: 33654293
Cell. 2015 May 21;161(5):1215-1228
pubmed: 26000489
Cell. 2014 Sep 25;159(1):176-187
pubmed: 25201530
Cancer Cell. 2021 Nov 8;39(11):1479-1496.e18
pubmed: 34653364
Cell. 2015 Oct 8;163(2):394-405
pubmed: 26435104
Nat Genet. 2020 Sep;52(9):908-918
pubmed: 32807988
Science. 2017 Jan 6;355(6320):78-83
pubmed: 28059767
Nat Med. 2020 Feb;26(2):259-269
pubmed: 32042191
Nat Rev Immunol. 2021 Sep;21(9):548-569
pubmed: 33833439
Nat Biotechnol. 2019 Apr;37(4):451-460
pubmed: 30899105
Nat Methods. 2020 Feb;17(2):159-162
pubmed: 31819264
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Biotechnol. 2016 May;34(5):525-7
pubmed: 27043002
Nat Cell Biol. 2021 Sep;23(9):1023-1034
pubmed: 34489572
J Clin Invest. 2019 Jul 30;129(10):4492-4505
pubmed: 31361600
Cancer Discov. 2014 Jul;4(7):816-27
pubmed: 24771846
Nat Rev Cancer. 2015 Dec;15(12):701-11
pubmed: 26563462
Genome Biol. 2018 Feb 6;19(1):15
pubmed: 29409532
Genome Biol. 2019 Dec 23;20(1):296
pubmed: 31870423
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Front Bioeng Biotechnol. 2020 Mar 20;8:220
pubmed: 32266244
Cancer Cell. 2007 Dec;12(6):559-71
pubmed: 18068632
Genome Biol. 2019 Mar 22;20(1):63
pubmed: 30902100
Science. 2022 May 27;376(6596):eabe1505
pubmed: 35617398
Nat Commun. 2021 Mar 31;12(1):1998
pubmed: 33790302
Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11428-11436
pubmed: 31061129
F1000Res. 2015 Dec 30;4:1521
pubmed: 26925227
Science. 2017 Jan 6;355(6320):84-88
pubmed: 28059768
Genome Biol. 2019 Oct 11;20(1):206
pubmed: 31604482
Nat Protoc. 2016 Feb;11(2):347-58
pubmed: 26797458
Cancer Discov. 2011 Nov;1(6):487-95
pubmed: 22389870
Lancet. 2020 Aug 1;396(10247):333-344
pubmed: 32738955
Cell. 2015 Jul 2;162(1):184-97
pubmed: 26095251
Nat Rev Clin Oncol. 2020 Jun;17(6):360-371
pubmed: 32152485
Nat Biotechnol. 2016 Jun;34(6):637-45
pubmed: 27136076
Elife. 2020 Sep 11;9:
pubmed: 32915138
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Cancer Cell. 2006 Oct;10(4):321-30
pubmed: 17010675
Nat Methods. 2014 Aug;11(8):783-784
pubmed: 25075903
Cancer Res. 2006 Aug 15;66(16):7889-98
pubmed: 16912162
Nat Methods. 2016 Oct;13(10):845-8
pubmed: 27571553
Science. 2020 May 1;368(6490):497-505
pubmed: 32355025
Nat Med. 2016 Mar;22(3):298-305
pubmed: 26855148
Immunity. 2020 Jan 14;52(1):183-199.e9
pubmed: 31924475
Cell. 2018 Aug 9;174(4):843-855.e19
pubmed: 30017245
JAMA Oncol. 2017 Dec 1;3(12):1663-1672
pubmed: 28494073
Cell. 2014 Oct 9;159(2):440-55
pubmed: 25263330
Clin Cancer Res. 2020 Jun 1;26(11):2654-2663
pubmed: 31911548
JAMA Oncol. 2018 Feb 01;4(2):217-224
pubmed: 29121144
Nature. 2019 Feb;566(7745):496-502
pubmed: 30787437
Sci Transl Med. 2011 Mar 23;3(75):75ra26
pubmed: 21430269
Cell. 2014 Sep 25;159(1):163-175
pubmed: 25201529
Nature. 2017 Jun 29;546(7660):671-675
pubmed: 28614298
N Engl J Med. 2021 Jun 24;384(25):2382-2393
pubmed: 34161704
Science. 2016 Apr 8;352(6282):189-96
pubmed: 27124452
Nat Med. 2021 Mar;27(3):426-433
pubmed: 33664492
Nature. 2018 Oct;562(7727):367-372
pubmed: 30283141
Nat Rev Cancer. 2018 Feb;18(2):117-127
pubmed: 29192213
Nat Commun. 2021 Jun 7;12(1):3372
pubmed: 34099734
Genome Biol. 2015 Dec 10;16:278
pubmed: 26653891
Blood Cancer J. 2021 Dec 4;11(12):193
pubmed: 34864823
Nat Protoc. 2020 Apr;15(4):1484-1506
pubmed: 32103204
Cancer Cell. 2017 Oct 9;32(4):474-489.e6
pubmed: 29017058