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PXD008382

PXD008382 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLinking FOXO3, NCOA3, and TCF7L2 to Ras pathway phenotypes through a genome-wide forward genetic screen in human colorectal cancer cellsLinking FOXO3, NCOA3, and TCF7L2 to Ras pathway phenotypes through a genome-wide forward genetic screen in human colorectal cancer cells
DescriptionBackground: The Ras pathway genes KRAS, BRAF or ERBBs have somatic mutations in ~60% of human colorectal carcinomas. At present, it is unknown whether the remaining cases lack mutations activating the Ras pathway, or whether they have acquired mutations in genes hitherto not known to belong to the pathway. Methods: To address the second possibility, and extend the compendium of Ras pathway genes, we used genome-wide transposon mutagenesis of two human colorectal cancer cell systems deprived of their activating KRAS or BRAF allele to identify genes enabling growth in low glucose, a Ras pathway phenotype, when targeted. Results: Of the 163 recurrently targeted genes in the two different genetic backgrounds, one third were known cancer genes and one-fifth had links to the EGFR/Ras/MAPK pathway. When compared to cancer genome sequencing datasets, 9 genes also mutated in human colorectal cancers were identified. Among these, stable knock-down of FOXO3, NCOA3, and TCF7L2 restored growth in low glucose but reduced MEK/MAPK phosphorylation, reduced anchorage-independent growth, and modulated expressions of GLUT1 and Ras pathway related proteins. Knock-down of NCOA3 and FOXO3 significantly decreased the sensitivity to cetuximab of KRAS mutant but not wild-type cells. Conclusions: This work establishes a proof-of-concept that human cell based genome-wide forward genetic screens can assign genes to pathways with clinical importance in human colorectal cancer.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:42:09.309.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJacek Wisniewski
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-12-07 02:08:34ID requested
12018-02-20 03:27:41announced
22024-10-22 04:42:17announced2024-10-22: Updated project metadata.
Publication List
Kundu S, Ali MA, Handin N, Padhan N, Larsson J, Karoutsou M, Ban K, Wi, ś, niewski JR, Artursson P, He L, Hellstr, ö, m M, Sj, ö, blom T, Linking FOXO3, NCOA3, and TCF7L2 to Ras pathway phenotypes through a genome-wide forward genetic screen in human colorectal cancer cells. Genome Med, 10(1):2(2018) [pubmed]
10.1186/s13073-017-0511-4;
Keyword List
curator keyword: Biomedical
submitter keyword: : Forward genetics, piggyBac transposon, Ras pathway, colorectal cancer
Contact List
Jacek R Wisniewski
contact affiliationBiochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, 82152-Martinsried, Germany
contact emailjwisniew@biochem.mpg.de
lab head
Jacek Wisniewski
contact affiliationProteomics
contact emailjwisniew@biochem.mpg.de
dataset submitter
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