PXD033636

PXD033636 is an original dataset announced via ProteomeXchange.

Title	Analysis of of the ole of NOMO1 in early-onset colorectal cancer (EOCRC)
Description	Early-onset colorectal cancer (EOCRC; age younger than 50 years) incidence has been steadily increasing over the last decades worldwide with causes unexplained. A unique molecular feature of EOCRC is that these cases harbor a greater incidence of Nodal Modulator 1 (NOMO1) somatic deletions compared with late-onset CRC. Yet the mechanisms of NOMO1 in early-onset colorectal carcinogenesis are currently unknown. Here we show that 50% of heterozygous NOMO1 deleted–EOCRCs presented pathogenic mutations in this gene, suggesting that NOMO1 can be inactivated by deletion or mutation in EOCRC. To study its role in EOCRC, CRISPR/cas9 technology was used to generate NOMO1 knockout HCT-116 (EOCRC) and HS-5 (bone marrow) cell lines. Loss of NOMO1 in these cell lines did not perturb Nodal pathway signaling. Results from expression microarray, RNA sequencing and protein expression analysis by LC-IMS/MS revealed that NOMO1 inactivation deregulates other signaling pathways independent of the Nodal pathway such as epithelial-mesenchymal transition. Importantly, NOMO1 inactivation increased the migration capacity of CRC cells. Additionally, a gut-specific conditional KO mouse model of NOMO1 revealed no subsequent tumor development in mice. Overall, these findings suggest that NOMO1 could not be a driver of early-onset colorectal carcinogenesis, but its loss promotes an increased migration capacity of CRC cells. Further study is warranted to explore other signaling pathways deregulated by the loss of NOMO1 that may play a relevant role in the pathogenesis of the disease.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:29:31.669.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mikel Azkargorta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-04 14:36:31	ID requested
1	2022-10-14 22:29:05	announced
⏵ 2	2023-11-14 07:29:36	announced	2023-11-14: Updated project metadata.

P, é, rez-Garc, í, a J, Martel-Martel A, Garc, í, a-Vall, é, s P, Corchete LA, Garc, í, a JL, Gestoso-Uzal N, Vidal-Tocino R, Blanco Ó, M, é, ndez L, S, á, nchez-Mart, í, n M, Fuentes M, Herrero AB, Holowatyj AN, Perea J, Gonz, á, lez-Sarmiento R, Gene Deletion Is a Potential Clinical Marker in Early-Onset Colorectal Cancer and Is Involved in the Regulation of Cell Migration. Cancers (Basel), 14(16):(2022) [pubmed]

submitter keyword: Colorectal cancer,EOCRC, label free

Felix Elortza
contact affiliation	Protomic Service CIC bioGUNE Bizkaia Tech. Park Build. 800 Derio 48160 Spain
contact email	felorta@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliation	Proteomics Platform CIC bioGUNE
contact email	mazkargorta@cicbiogune.es
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/2022/10/PXD033636

PRIDE project URI

• PRIDE
  1. PXD033636
     1. Label: PRIDE project
     2. Name: Analysis of of the ole of NOMO1 in early-onset colorectal cancer (EOCRC)