Multiomics of Colorectal Cancer Organoids Reveals Putative Mediators of Cancer Progression Resulting from SMAD4 Inactivation.
SMAD4
cancer progression
colorectal cancer
multiomics
secretomics
Journal
Journal of proteome research
ISSN: 1535-3907
Titre abrégé: J Proteome Res
Pays: United States
ID NLM: 101128775
Informations de publication
Date de publication:
06 01 2023
06 01 2023
Historique:
pubmed:
1
12
2022
medline:
10
1
2023
entrez:
30
11
2022
Statut:
ppublish
Résumé
The development of metastasis severely reduces the life expectancy of patients with colorectal cancer (CRC). Although loss of SMAD4 is a key event in CRC progression, the resulting changes in biological processes in advanced disease and metastasis are not fully understood. Here, we applied a multiomics approach to a CRC organoid model that faithfully reflects the metastasis-supporting effects of SMAD4 inactivation. We show that loss of SMAD4 results in decreased differentiation and activation of pro-migratory and cell proliferation processes, which is accompanied by the disruption of several key oncogenic pathways, including the TGFβ, 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
Identifiants
pubmed: 36450103
doi: 10.1021/acs.jproteome.2c00551
pmc: PMC9830641
doi:
Substances chimiques
Transforming Growth Factor beta
0
Smad4 Protein
0
SMAD4 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
138-151Références
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