PXD024502-1

PXD024502 is an original dataset announced via ProteomeXchange.

Title	Loss of enteric neuronal Ndrg4 promotes colorectal cancer via increased release of Nid1 and Fbln2
Description	The N-Myc Downstream-Regulated Gene 4 (NDRG4), a prominent biomarker for colorectal cancer (CRC), is specifically expressed by enteric neurons. Considering that nerves are important members of the tumor microenvironment, we here establish different Ndrg4 knockout (Ndrg4-/-) CRC models and an in-direct co-culture of primary enteric nervous system (ENS) cells and intestinal organoids to identify whether the ENS, via NDRG4, affects intestinal tumorigenesis. Linking immunostainings and gastrointestinal motility (GI) assays, we show that absence of Ndrg4 does not trigger any functional or morphological GI-abnormalities. However, combining in vivo, in vitro and quantitative proteomics data, we uncover that Ndrg4 knockdown is associated with enlarged intestinal adenoma development and that organoid growth is boosted by the Ndrg4-/- ENS cell secretome, which is enriched for Nidogen-1 (Nid1) and Fibulin-2 (Fbln2). Moreover, NID1 and FBLN2 are expressed in enteric neurons, enhance tumorigenic capacities of CRC cells and are enriched in human CRC secretomes. Hence, we provide evidence that the ENS, via loss of Ndrg4, is involved in colorectal pathogenesis and that ENS-derived Nidogen-1 and Fibulin-2 enhance colorectal carcinogenesis.
HostingRepository	PRIDE
AnnounceDate	2021-04-23
AnnouncementXML	Submission_2021-04-23_04:14:31.239.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeroen Demmers
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-03 08:52:11	ID requested
⏵ 1	2021-04-23 04:14:31	announced

Dataset with its publication pending

submitter keyword: Ndrg4, extracellular matrix proteins, Nidogen-1, Fibulin-2

Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus University Medical Center
contact email	j.demmers@erasmusmc.nl
lab head
Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact email	j.demmers@erasmusmc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024502
     1. Label: PRIDE project
     2. Name: Loss of enteric neuronal Ndrg4 promotes colorectal cancer via increased release of Nid1 and Fbln2