PXD008382

PXD008382 is an original dataset announced via ProteomeXchange.

Title	Linking 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
Description	Background: 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:42:09.309.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jacek Wisniewski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-12-07 02:08:34	ID requested
1	2018-02-20 03:27:41	announced
⏵ 2	2024-10-22 04:42:17	announced	2024-10-22: Updated project metadata.

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;

curator keyword: Biomedical

submitter keyword: : Forward genetics, piggyBac transposon, Ras pathway, colorectal cancer

Jacek R Wisniewski
contact affiliation	Biochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, 82152-Martinsried, Germany
contact email	jwisniew@biochem.mpg.de
lab head
Jacek Wisniewski
contact affiliation	Proteomics
contact email	jwisniew@biochem.mpg.de
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/2018/02/PXD008382

PRIDE project URI

• PRIDE
  1. PXD008382
     1. Label: PRIDE project
     2. Name: Linking 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