PXD022207

PXD022207 is an original dataset announced via ProteomeXchange.

Title	Heat Shock Factor 1-dependent extraceHeat Shock Factor 1-dependent extracellular matrix remodeling mediates the transition from chronic intestinal inflammation to colon cancerllular matrix remodeling mediates the transition from chronic intestinal inflammation to colon cancer
Description	Chronic inflammation underlies tumor initiation, progression, invasion, and metastasis. In the colon, long-term exposure to chronic inflammation drives colitis associated colon cancer (CAC) in patients with inflammatory bowel disease (IBD). While the causal and clinical links between chronic inflammation and CAC are well established, our molecular understanding of how chronic inflammation leads to the development of colon cancer is still lacking. Here we deconstruct the evolving microenvironment of CAC, by measuring proteomic changes and extracellular matrix (ECM) organization over time in a genetically modified mouse model of CAC. We detect early changes in ECM structure and composition, and report that the transcriptional regulator heat shock factor 1 (HSF1) plays a crucial role in orchestrating these events. Activated in stromal fibroblasts of the gut, HSF1 promotes ECM remodeling and inflammatory programs which lead to the development of CAC. Loss of HSF1 abrogates ECM assembly by colon fibroblasts in cell culture, prevents inflammation-induced ECM remodeling in mice and significantly inhibits progression to CAC. Establishing the relevance of our experimental findings 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.
HostingRepository	PRIDE
AnnounceDate	2020-11-05
AnnouncementXML	Submission_2020-11-04_23:37:13.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	hagar lavon
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-27 08:12:41	ID requested
⏵ 1	2020-11-04 23:37:14	announced

Dataset with its publication pending

submitter keyword: tumor microenvironmnet, cancer, cancer associated fibroblasts,colon cancer, HSF1, ECM

Ruth Scherz-Shouval
contact affiliation	Bio-molecular sciences, The Weizmann Institue of Science, Israel
contact email	ruth.shouval@weizmann.ac.il
lab head
hagar lavon
contact affiliation	The Weizmann institute of science
contact email	hagar.lavon@weizmann.ac.il
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/11/PXD022207

PRIDE project URI

• PRIDE
  1. PXD022207
     1. Label: PRIDE project
     2. Name: Heat Shock Factor 1-dependent extraceHeat Shock Factor 1-dependent extracellular matrix remodeling mediates the transition from chronic intestinal inflammation to colon cancerllular matrix remodeling mediates the transition from chronic intestinal inflammation to colon cancer