PXD036441

PXD036441 is an original dataset announced via ProteomeXchange.

Title	Multi-omics of colon tumor progression organoids reveals putative mediators of colorectal cancer metastasis
Description	The development of metastasis severely reduces the life expectancy of patients with colorectal cancer (CRC). Loss of SMAD4 is a key event in late-stage CRC resulting in the progression to metastatic CRC in 10-30% of the cases. However, the biological processes and underlying molecular mechanisms that it affects are not fully understood. Here, we applied a multi-omics approach to a CRC tumor progression organoid model that faithfully reflects the metastasis-inducing effects of SMAD4 inactivation. We show that loss of SMAD4 results in loss of differentiation and activation of pro-migratory and cell proliferation processes, which is accompanied by the disruption of several key oncogenic pathways, including the TGFB, WNT, and VEGF pathways. In addition, SMAD4 inactivation leads to increased secretion of proteins that are known to be involved in a variety of pro-metastatic processes. Finally, we show that one of the factors that is specifically secreted by metastatic organoids – DKK3 – reduces the anti-tumor effects of natural killer cells (NKCs). Altogether, our data provides promising new targets concerning the role of SMAD4 perturbation and metastatic disease in CRC.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:27:35.156.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jelmer Dijkstra
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-01 02:07:03	ID requested
1	2022-12-10 17:41:13	announced
⏵ 2	2023-11-14 07:27:38	announced	2023-11-14: Updated project metadata.

Dijkstra JJ, Neikes HK, Rezaeifard S, Ma X, Voest EE, Tauriello DVF, Vermeulen M, Multiomics of Colorectal Cancer Organoids Reveals Putative Mediators of Cancer Progression Resulting from SMAD4 Inactivation. J Proteome Res, 22(1):138-151(2023) [pubmed]

submitter keyword: Whole-cell proteomics, secretomics, colon cancer, SMAD4, metastasis

Michiel Vermeulen
contact affiliation	Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Oncode Institute, Radboud University Nijmegen, Nijmegen, The Netherlands
contact email	Michiel.Vermeulen@science.ru.nl
lab head
Jelmer Dijkstra
contact affiliation	RIMLS
contact email	jelmer.dijkstra@science.ru.nl
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/2022/12/PXD036441

PRIDE project URI

• PRIDE
  1. PXD036441
     1. Label: PRIDE project
     2. Name: Multi-omics of colon tumor progression organoids reveals putative mediators of colorectal cancer metastasis