Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 02 2023
11 02 2023
Historique:
received:
29
07
2021
accepted:
31
01
2023
entrez:
11
2
2023
pubmed:
12
2
2023
medline:
15
2
2023
Statut:
epublish
Résumé
The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply this approach to explore EMT trajectories in 7180 tumours of epithelial origin and identify three macro-states with prognostic and therapeutic value, attributable to epithelial, hybrid E/M and mesenchymal phenotypes. We show that the hybrid state is relatively stable and linked with increased aneuploidy. We further employ spatial transcriptomics and single cell datasets to explore the spatial heterogeneity of EMT transformation and distinct interaction patterns with cytotoxic, NK cells and fibroblasts in the tumour microenvironment. Additionally, we provide a catalogue of genomic events underlying distinct evolutionary constraints on EMT transformation. This study sheds light on the aetiology of distinct stages along the EMT trajectory, and highlights broader genomic and environmental hallmarks shaping the mesenchymal transformation of primary tumours.
Identifiants
pubmed: 36774358
doi: 10.1038/s41467-023-36439-7
pii: 10.1038/s41467-023-36439-7
pmc: PMC9922305
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
789Subventions
Organisme : Medical Research Council
ID : MR/T042184/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
Références
Cancers (Basel). 2019 Oct 16;11(10):
pubmed: 31623163
Br J Cancer. 2010 Jan 19;102(2):428-35
pubmed: 20087356
Mol Cancer. 2018 Feb 19;17(1):42
pubmed: 29455655
Br J Cancer. 2020 May;122(10):1477-1485
pubmed: 32203224
Cell. 2008 May 16;133(4):704-15
pubmed: 18485877
Cancers (Basel). 2018 Mar 19;10(3):
pubmed: 29562660
NPJ Precis Oncol. 2021 Jun 16;5(1):52
pubmed: 34135436
Nature. 2012 Mar 28;483(7391):603-7
pubmed: 22460905
Int J Oncol. 2018 Aug;53(2):620-632
pubmed: 29767249
Biostatistics. 2007 Jan;8(1):118-27
pubmed: 16632515
Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):E2977-86
pubmed: 23882083
Commun Biol. 2020 Oct 9;3(1):565
pubmed: 33037292
Dev Cell. 2019 Feb 25;48(4):539-553.e6
pubmed: 30713070
Front Oncol. 2015 Jul 20;5:155
pubmed: 26258068
Cancer Cell. 2018 Apr 9;33(4):676-689.e3
pubmed: 29622463
J Clin Invest. 2009 Jun;119(6):1420-8
pubmed: 19487818
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Mol Cell Oncol. 2018 Mar 7;5(3):e1448244
pubmed: 30250901
Trends Cell Biol. 2019 Mar;29(3):212-226
pubmed: 30594349
Philos Trans R Soc Lond B Biol Sci. 2020 Oct 12;375(1809):20200087
pubmed: 32829692
Nat Commun. 2019 Jul 5;10(1):2983
pubmed: 31278301
Nat Commun. 2019 Dec 6;10(1):5587
pubmed: 31811131
Nature. 2017 Aug 17;548(7667):297-303
pubmed: 28783718
Nature. 2009 Jul 9;460(7252):278-82
pubmed: 19506557
Cancers (Basel). 2021 Mar 20;13(6):
pubmed: 33804802
Nat Methods. 2022 Feb;19(2):171-178
pubmed: 35102346
Cell Biosci. 2011 Aug 31;1:29
pubmed: 21880137
Clin Cancer Res. 2016 Feb 1;22(3):609-20
pubmed: 26420858
Front Immunol. 2021 Dec 15;12:797261
pubmed: 34975907
Dev Cell. 2020 Feb 24;52(4):413-428.e6
pubmed: 32097652
Genome Biol. 2018 Feb 6;19(1):15
pubmed: 29409532
Cell. 2021 Jun 24;184(13):3573-3587.e29
pubmed: 34062119
Ann Transl Med. 2019 Apr;7(7):127
pubmed: 31157248
Sci Rep. 2018 Feb 13;8(1):2918
pubmed: 29440769
Nat Cell Biol. 2011 Mar;13(3):317-23
pubmed: 21336307
Cell Res. 2020 Sep;30(9):745-762
pubmed: 32561858
Cell Cycle. 2011 May 15;10(10):1563-70
pubmed: 21502814
Mol Oncol. 2017 Jul;11(7):755-769
pubmed: 28548345
Dev Cell. 2018 Jun 18;45(6):681-695.e4
pubmed: 29920274
Oncogene. 2011 Jan 6;30(1):21-31
pubmed: 20802534
Cancer Cell Int. 2021 Jan 20;21(1):62
pubmed: 33472628
PLoS Comput Biol. 2019 Mar 11;15(3):e1006832
pubmed: 30856170
Gastroenterology Res. 2019 Dec;12(6):275-282
pubmed: 31803306
Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96
pubmed: 24556840
Nature. 2020 Feb;578(7793):94-101
pubmed: 32025018
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Nat Commun. 2017 May 05;8:15081
pubmed: 28474673
Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1978-83
pubmed: 11830638
Nat Genet. 2019 Sep;51(9):1389-1398
pubmed: 31477929
Proc Natl Acad Sci U S A. 2019 Apr 30;116(18):9020-9029
pubmed: 30996127
Br J Cancer. 2014 Feb 4;110(3):724-32
pubmed: 24335925
BMC Genomics. 2020 Jul 14;21(1):482
pubmed: 32664861
Cell. 2018 Apr 5;173(2):400-416.e11
pubmed: 29625055
Nat Commun. 2021 May 10;12(1):2592
pubmed: 33972543
Nature. 2018 Apr;556(7702):463-468
pubmed: 29670281
Cell. 2009 Nov 25;139(5):871-90
pubmed: 19945376
Cancer Res. 2022 Jul 5;82(13):2329-2343
pubmed: 35363853
Nat Commun. 2018 Jun 20;9(1):2419
pubmed: 29925878
Cancer Res. 2019 Dec 15;79(24):6238-6246
pubmed: 31641033
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
Sci Rep. 2017 Nov 21;7(1):15918
pubmed: 29162839
Nucleic Acids Res. 2016 May 5;44(8):e71
pubmed: 26704973
J Biochem. 2011 Jun;149(6):633-9
pubmed: 21478191
Cell. 2012 Jan 20;148(1-2):349-61
pubmed: 22265420
Cell. 2017 Dec 14;171(7):1611-1624.e24
pubmed: 29198524
Cell. 2018 Apr 5;173(2):291-304.e6
pubmed: 29625048
Nature. 2020 Dec;588(7837):331-336
pubmed: 33299191
Cell. 2021 Oct 14;184(21):5306-5308
pubmed: 34653367
BMC Cancer. 2019 Oct 16;19(1):963
pubmed: 31619201
Sci Rep. 2016 Jun 03;6:27072
pubmed: 27255191
Nat Commun. 2020 May 1;11(1):2142
pubmed: 32358524
Nat Cancer. 2020 Apr;1(4):372-373
pubmed: 35121968
Oncogene. 2022 Feb;41(6):824-837
pubmed: 34857888
PLoS Comput Biol. 2015 Nov 10;11(11):e1004569
pubmed: 26554584
Nat Cell Biol. 2019 Jan;21(1):102-112
pubmed: 30602760
J Cancer. 2021 Oct 17;12(23):7120-7129
pubmed: 34729113
J Exp Clin Cancer Res. 2014 May 30;33:47
pubmed: 24886365
Stem Cell Reports. 2019 Apr 9;12(4):743-756
pubmed: 30880078
Genome Biol. 2016 Feb 22;17:31
pubmed: 26899170
Nat Protoc. 2020 Apr;15(4):1484-1506
pubmed: 32103204
Dev Dyn. 2018 Mar;247(3):555-564
pubmed: 28073171
Oncotarget. 2016 Apr 26;7(17):24688-99
pubmed: 27029057
Mol Oncol. 2017 Jul;11(7):824-846
pubmed: 28614624
PLoS Comput Biol. 2020 Mar 10;16(3):e1007682
pubmed: 32155144
Nat Genet. 2019 Feb;51(2):308-318
pubmed: 30643250
Front Genet. 2019 Sep 25;10:858
pubmed: 31608109
J Exp Clin Cancer Res. 2019 Jan 28;38(1):38
pubmed: 30691517
Cell. 2017 Nov 16;171(5):1029-1041.e21
pubmed: 29056346
Nat Commun. 2023 Feb 11;14(1):789
pubmed: 36774358
Cell. 2016 Jul 28;166(3):740-754
pubmed: 27397505
Nat Commun. 2021 Oct 14;12(1):6012
pubmed: 34650042