Heat Shock Factor 1-dependent extracellular matrix remodeling mediates the transition from chronic intestinal inflammation to colon cancer.
Animals
Cell Line, Tumor
Cells, Cultured
Colitis-Associated Neoplasms
/ genetics
Disease Models, Animal
Extracellular Matrix
/ metabolism
Heat Shock Transcription Factors
/ genetics
Humans
Mass Spectrometry
/ methods
Mice, 129 Strain
Mice, Inbred BALB C
Mice, Knockout
Proteome
/ genetics
Proteomics
/ methods
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 12 2020
07 12 2020
Historique:
received:
21
09
2020
accepted:
09
11
2020
entrez:
8
12
2020
pubmed:
9
12
2020
medline:
29
12
2020
Statut:
epublish
Résumé
In the colon, long-term exposure to chronic inflammation drives colitis-associated colon cancer (CAC) in patients with inflammatory bowel disease. While the causal and clinical links are well established, molecular understanding of how chronic inflammation leads to the development of colon cancer is lacking. Here we deconstruct the evolving microenvironment of CAC by measuring proteomic changes and extracellular matrix (ECM) organization over time in a mouse model of CAC. We detect early changes in ECM structure and composition, and report a crucial role for the transcriptional regulator heat shock factor 1 (HSF1) in orchestrating these events. Loss of HSF1 abrogates ECM assembly by colon fibroblasts in cell-culture, prevents inflammation-induced ECM remodeling in mice and inhibits progression to CAC. Establishing relevance to human disease, we find high activation of stromal HSF1 in CAC patients, and detect the HSF1-dependent proteomic ECM signature in human colorectal cancer. Thus, HSF1-dependent ECM remodeling plays a crucial role in mediating inflammation-driven colon cancer.
Identifiants
pubmed: 33288768
doi: 10.1038/s41467-020-20054-x
pii: 10.1038/s41467-020-20054-x
pmc: PMC7721883
doi:
Substances chimiques
Heat Shock Transcription Factors
0
Proteome
0
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
6245Subventions
Organisme : Cancer Research UK
ID : FC010144
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC010144
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : U01 TR002625
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118173
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Medical Research Council
ID : FC010144
Pays : United Kingdom
Références
Int J Biochem Cell Biol. 2014 Dec;57:76-83
pubmed: 25450459
Bioinformatics. 2013 Jul 15;29(14):1840-1
pubmed: 23681123
EBioMedicine. 2015 Sep 14;2(11):1600-6
pubmed: 26870784
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Biol Chem. 2007 Nov 9;282(45):33210-7
pubmed: 17766920
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
Gastroenterology. 2016 Aug;151(2):278-287.e6
pubmed: 27063727
J Leukoc Biol. 1993 Feb;53(2):197-204
pubmed: 8445331
Nat Protoc. 2019 Dec;14(12):3395-3425
pubmed: 31705125
Trends Biochem Sci. 2019 Nov;44(11):927-942
pubmed: 31303384
Gastroenterology. 2016 Apr;150(4):931-43
pubmed: 26764183
J Biol Chem. 2007 Aug 10;282(32):23240-52
pubmed: 17556362
Lab Invest. 1993 Aug;69(2):238-49
pubmed: 8350599
Gastroenterology. 2015 Oct;149(5):1275-1285.e2
pubmed: 26166315
Cell. 2004 Aug 6;118(3):285-96
pubmed: 15294155
J Am Chem Soc. 2019 Jan 23;141(3):1312-1323
pubmed: 30590924
Biomaterials. 2016 Oct;104:52-64
pubmed: 27424216
Cell. 2012 Aug 3;150(3):549-62
pubmed: 22863008
Br J Cancer. 2009 Aug 4;101(3):492-7
pubmed: 19603022
Mol Cell Proteomics. 2012 Apr;11(4):M111.014647
pubmed: 22159717
Int J Mol Sci. 2019 Nov 19;20(22):
pubmed: 31752429
Cancer Cell. 2010 Feb 17;17(2):135-47
pubmed: 20138012
Cell Mol Life Sci. 2008 Mar;65(6):855-61
pubmed: 18239856
J Biol Chem. 1990 Jul 15;265(20):11421-4
pubmed: 2164002
J Am Chem Soc. 2015 Jan 14;137(1):525-30
pubmed: 25514979
Nat Methods. 2019 Dec;16(12):1226-1232
pubmed: 31570887
FASEB J. 2019 Feb;33(2):2621-2635
pubmed: 30307772
Nat Med. 2008 May;14(5):518-27
pubmed: 18438415
Nucleic Acids Res. 2019 Jul 2;47(W1):W191-W198
pubmed: 31066453
J Vis Exp. 2013 Oct 12;(80):
pubmed: 24145735
Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18378-83
pubmed: 22042860
Cell. 2007 Sep 21;130(6):1005-18
pubmed: 17889646
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Nat Rev Mol Cell Biol. 2014 Dec;15(12):786-801
pubmed: 25415508
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Cancer Res. 2015 Aug 15;75(16):3255-67
pubmed: 26122846
Nat Cell Biol. 2018 Jul;20(7):766-774
pubmed: 29950570
Bioinformatics. 2016 Nov 15;32(22):3532-3534
pubmed: 27412086
Nat Commun. 2019 Jan 10;10(1):130
pubmed: 30631061
Nat Protoc. 2007;2(8):1998-2004
pubmed: 17703211
BMC Cancer. 2014 Jul 18;14:518
pubmed: 25037231
Nat Rev Cancer. 2020 Mar;20(3):174-186
pubmed: 31980749
Trends Cell Biol. 2017 Dec;27(12):895-905
pubmed: 28890254
Sci Rep. 2017 Dec 15;7(1):17617
pubmed: 29247221
Trends Endocrinol Metab. 2017 May;28(5):388-397
pubmed: 28214071
Nat Protoc. 2006;1(6):2900-4
pubmed: 17406549
Mol Ther. 2018 Jul 5;26(7):1828-1839
pubmed: 29730197
Cell. 2014 Jul 31;158(3):564-78
pubmed: 25083868
Curr Protoc Cell Biol. 2016 Jun 01;71:10.9.1-10.9.34
pubmed: 27245425
J Immunol. 2010 Jan 15;184(2):1041-8
pubmed: 20018623
Cancer Discov. 2018 Mar;8(3):304-319
pubmed: 29196464
Nat Med. 2011 Mar;17(3):320-9
pubmed: 21383745
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
J Biol Chem. 2002 Feb 15;277(7):4981-8
pubmed: 11734555
Cancer Cell. 2013 May 13;23(5):634-46
pubmed: 23680148
Science. 2013 Jul 19;341(6143):1238303
pubmed: 23869022
Cancer Res. 2016 Jul 15;76(14):4249-58
pubmed: 27221706
Oncotarget. 2017 Dec 12;9(1):969-981
pubmed: 29416670
Front Pharmacol. 2014 May 27;5:123
pubmed: 24904424
Curr Opin Cell Biol. 2016 Oct;42:80-93
pubmed: 27214794
Matrix Biol. 2016 Jan;49:10-24
pubmed: 26163349
Nat Rev Mol Cell Biol. 2002 May;3(5):349-63
pubmed: 11988769
Gastroenterology. 2017 Apr;152(5):964-979
pubmed: 28111227
Lab Invest. 2008 Jun;88(6):591-601
pubmed: 18414401
Mol Carcinog. 1991;4(6):527-33
pubmed: 1793490
Nat Methods. 2016 Sep;13(9):731-40
pubmed: 27348712
J Biol Chem. 1998 Mar 27;273(13):7523-8
pubmed: 9516453
Nucleic Acids Res. 2020 Jan 8;48(D1):D1136-D1144
pubmed: 31586405