PXD010252

PXD010252 is an original dataset announced via ProteomeXchange.

Title	Liver metastatic growth in colorectal cancer depends on PAD4 leading to modification of the extracellular matrix by citrullination
Description	Colorectal cancer is one of the most frequently occurring malignancies and a major cause of cancer death. Distant metastases in this disease most commonly develop in the liver and are often untreatable. Here, we show that citrullination of the extracellular matrix (ECM) by cancer cell derived peptidylarginine deiminase 4 (PAD4) is essential for the growth of liver metastases. Citrullination of proteins, a post-translational conversion of arginine residues to citrulline, is well recognized in rheumatoid arthritis, but largely undocumented in cancer. PAD4, a key enzyme responsible for catalyzing citrullination, is produced by metastatic colorectal cancer cells and found at higher levels in human liver metastases than in normal liver. Functional significance for citrullination in metastatic growth was evident in murine models where inhibition of citrullination, either globally by pharmacologic inhibition of PADs or specifically in colorectal cancer cells by PAD4 knockdown substantially reduced liver metastatic burden. Additionally, citrullination of a key ECM component collagen type I led to greater adhesion and decreased migration of colorectal cancer cells along with increased expression of characteristic epithelial markers, suggesting a role for citrullination in promoting mesenchymal-to-epithelial transition (MET) and liver metastasis. Overall, our study revealed the potential for PAD4-dependant citrullination to drive the progression of liver metastasis. These data indicate that inhibition of citrullination could be exploited to prevent the development of liver metastases in colorectal cancer.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:46:11.972.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD010252
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; Carbamidomethyl
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-27 08:17:53	ID requested
1	2018-10-18 11:43:04	announced
⏵ 2	2024-10-22 04:46:12	announced	2024-10-22: Updated project metadata.

10.6019/PXD010252;

curator keyword: Biological

submitter keyword: Citrullination,Liver, PAD4

Roman Fischer
contact affiliation	Discovery Proteomics Facility, Oxford
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010252
     1. Label: PRIDE project
     2. Name: Liver metastatic growth in colorectal cancer depends on PAD4 leading to modification of the extracellular matrix by citrullination