PXD033440-2

PXD033440 is an original dataset announced via ProteomeXchange.

Title	Loss of colonic primary cilia promotes inflammation and carcinogenesis
Description	Primary cilia (PC) are important signaling hubs in cells and we explored their role in colorectal cancer (CRC) and colitis. In the colon we found PC to be mostly present on different subtypes of fibroblasts and exposure of mice to either chemically induced colitis-associated colon carcinogenesis (CAC) or dextran sodium sulfate (DSS)-induced acute colitis decreased PC numbers. We employed conditional knock-out strains for the PC essential genes, Kif3A and Ift88, to generate mice with reduced numbers of PC on colonic fibroblasts. These mice showed an increased susceptibility in the CAC model as well as in DSS-induced colitis. Secretome and immunohistochemical analyses of DSS-treated mice displayed an elevated production of the pro-inflammatory cytokine IL-6 in PC-deficient colons. An inflammatory environment diminished PC presence in primary fibroblast cultures. This was triggered by IL-6 as identified by RNAseq analysis together with blocking experiments, suggesting an activation loop between IL-6 production and PC loss. Notably, an analysis of PC presence on biopsies of patients with ulcerative colitis as well as CRC patients revealed decreased numbers of PC on colonic fibroblasts in pathological versus surrounding normal tissue. Taken together, we provide evidence that a decrease in colonic PC numbers promotes colitis and CRC.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:56:08.957.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maria Concetta Cufaro
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-25 01:54:19	ID requested
1	2022-11-29 05:37:14	announced
⏵ 2	2023-11-14 08:56:09	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: colon carcinogenesis, inflammation,Primary cilia, colonic fibroblasts, colitis

Damiana Pieragostino
contact affiliation	Department of Innovative Technologies in Medicine & Dentistry, University of Chieti, Italy
contact email	damia.pieragostino@unich.it
lab head
Maria Concetta Cufaro
contact affiliation	University "G. d'Annunzio" of Chieti
contact email	maria.cufaro@unich.it
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/2022/11/PXD033440

PRIDE project URI

• PRIDE
  1. PXD033440
     1. Label: PRIDE project
     2. Name: Loss of colonic primary cilia promotes inflammation and carcinogenesis