Cancer-associated fibroblasts are the main contributors to epithelial-to-mesenchymal signatures in the tumor microenvironment.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 02 2023
21 02 2023
Historique:
received:
05
04
2022
accepted:
19
01
2023
entrez:
22
2
2023
pubmed:
23
2
2023
medline:
25
2
2023
Statut:
epublish
Résumé
Epithelial-to-mesenchymal transition (EMT) is associated with tumor initiation, metastasis, and drug resistance. However, the mechanisms underlying these associations are largely unknown. We studied several tumor types to identify the source of EMT gene expression signals and a potential mechanism of resistance to immuno-oncology treatment. Across tumor types, EMT-related gene expression was strongly associated with expression of stroma-related genes. Based on RNA sequencing of multiple patient-derived xenograft models, EMT-related gene expression was enriched in the stroma versus parenchyma. EMT-related markers were predominantly expressed by cancer-associated fibroblasts (CAFs), cells of mesenchymal origin which produce a variety of matrix proteins and growth factors. Scores derived from a 3-gene CAF transcriptional signature (COL1A1, COL1A2, COL3A1) were sufficient to reproduce association between EMT-related markers and disease prognosis. Our results suggest that CAFs are the primary source of EMT signaling and have potential roles as biomarkers and targets for immuno-oncology therapies.
Identifiants
pubmed: 36810872
doi: 10.1038/s41598-023-28480-9
pii: 10.1038/s41598-023-28480-9
pmc: PMC9944255
doi:
Substances chimiques
Collagen Type I, alpha2 Subunit
0
Collagen Type I
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3051Informations de copyright
© 2023. The Author(s).
Références
Nature. 2012 Jul 26;487(7408):500-4
pubmed: 22763439
Cancer Res. 2016 Jul 15;76(14):4124-35
pubmed: 27216177
Nat Med. 2015 Nov;21(11):1318-25
pubmed: 26479923
Nat Commun. 2016 Jun 08;7:11762
pubmed: 27272654
J Immunol. 2005 May 1;174(9):5215-23
pubmed: 15843517
Science. 2013 Feb 1;339(6119):580-4
pubmed: 23372014
Nat Commun. 2020 Nov 4;11(1):5583
pubmed: 33149148
Nature. 2018 Feb 22;554(7693):544-548
pubmed: 29443960
Nat Med. 2011 Oct 23;17(11):1514-20
pubmed: 22019887
Oncotarget. 2016 Feb 2;7(5):6159-74
pubmed: 26716418
Nat Immunol. 2019 Feb;20(2):163-172
pubmed: 30643263
Mol Oncol. 2013 Aug;7(4):776-90
pubmed: 23607916
Cancer Res. 2013 Aug 1;73(15):4885-97
pubmed: 23737486
Transl Oncol. 2020 Jun;13(6):100773
pubmed: 32334405
J Clin Invest. 2017 Aug 1;127(8):2930-2940
pubmed: 28650338
Cancer Discov. 2011 Nov;1(6):508-23
pubmed: 22586653
Biochem Pharmacol. 2021 Apr;186:114474
pubmed: 33607074
J Biol Chem. 2001 May 18;276(20):17058-62
pubmed: 11279127
Sci Transl Med. 2012 Jun 6;4(137):137ra75
pubmed: 22674553
Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20212-7
pubmed: 24277834
Signal Transduct Target Ther. 2021 Jun 10;6(1):218
pubmed: 34108441
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5262-70
pubmed: 17875754
Nat Commun. 2018 Aug 29;9(1):3503
pubmed: 30158554
QJM. 2019 Aug 1;112(8):581-590
pubmed: 31106370
Clin Cancer Res. 2016 Feb 1;22(3):609-20
pubmed: 26420858
Dev Cell. 2019 May 6;49(3):361-374
pubmed: 31063755
BMC Bioinformatics. 2007 Jul 12;8:250
pubmed: 17626636
Genome Biol. 2019 Dec 23;20(1):296
pubmed: 31870423
Cell. 2016 Mar 24;165(1):35-44
pubmed: 26997480
Nat Rev Cancer. 2018 Feb;18(2):128-134
pubmed: 29326430
Cancer Res. 2015 Jul 15;75(14):2800-2810
pubmed: 25979873
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Oncotarget. 2016 Apr 26;7(17):23282-99
pubmed: 26943036
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
J Hematol Oncol. 2019 Aug 28;12(1):86
pubmed: 31462327
Br J Cancer. 2022 Oct;127(6):1034-1042
pubmed: 35715633
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Nat Genet. 2017 May;49(5):708-718
pubmed: 28319088
Cancer Immunol Immunother. 2012 Jul;61(7):1019-31
pubmed: 22146893
Mol Cell Biol. 2009 Nov;29(22):6006-17
pubmed: 19752192
Cell. 2020 Apr 16;181(2):442-459.e29
pubmed: 32302573
Cancer Res. 2017 Sep 15;77(18):5142-5157
pubmed: 28687621
Hum Pathol. 2018 Sep;79:1-8
pubmed: 29555579
PLoS One. 2019 Feb 6;14(2):e0211117
pubmed: 30726287
PLoS One. 2017 Jul 27;12(7):e0179726
pubmed: 28749946
Cell. 2017 Dec 14;171(7):1611-1624.e24
pubmed: 29198524
Cancer Cell. 2010 Jun 15;17(6):547-59
pubmed: 20541700
J Cell Physiol. 2017 Dec;232(12):3261-3272
pubmed: 28079253
Hepatology. 2008 Jun;47(6):2059-67
pubmed: 18506891
J Clin Med. 2019 Sep 25;8(10):
pubmed: 31557977
Cell Mol Life Sci. 2020 Jun;77(11):2103-2123
pubmed: 31822964
BMC Cancer. 2012 Jan 24;12:35
pubmed: 22273460
Oncogene. 2006 Sep 7;25(40):5561-9
pubmed: 16619041
Sci Rep. 2019 Apr 19;9(1):6314
pubmed: 31004097
Nat Commun. 2013;4:2612
pubmed: 24113773
EMBO Mol Med. 2014 Sep 11;6(10):1279-93
pubmed: 25214461
Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12139-44
pubmed: 25092322
Clin Cancer Res. 2012 Oct 1;18(19):5314-28
pubmed: 22825584
Cell. 2016 Jun 30;166(1):21-45
pubmed: 27368099
J Transl Med. 2011 Nov 28;9:204
pubmed: 22123319
NPJ Precis Oncol. 2018 Nov 15;2:25
pubmed: 30456308
Mol Oncol. 2017 Jul;11(7):847-859
pubmed: 28544627
Sci Signal. 2014 Sep 23;7(344):re8
pubmed: 25249658