PXD007740-1

PXD007740 is an original dataset announced via ProteomeXchange.

Title	A system-wide approach to monitor responses to synergistic BRAF and EGFR inhibition in colorectal cancer cells
Description	Molecular heterogeneity of tumors, epigenetic changes and a diverse range of molecular mechanisms are main contributors to drug resistance, which represents one of the great challenges in cancer treatment. A deeper understanding of the molecular biology of cancer has resulted in better targeted therapies, where one or multiple drugs are adopted in novel therapies to tackle resistance. This beneficial effect of using combination treatments has to some extent also been observed in colorectal cancer (CRC) patients harboring the BRAF(V600E) mutation, whereby dual inhibition of BRAF(V600E) and EGFR increases antitumor activity. Notwithstanding this success, it is not clear whether this combination treatment is the only or most effective treatment to block resistance. Here, we investigate molecular responses upon single and multi-target treatments, over time, using BRAF(V600E) mutant CRC cells as a well-define model system. Through integration of transcriptomic, proteomic and phosphoproteomics data we obtain a comprehensive overview, revealing both well-known and novel responses. We primarily observe widespread upregulation of tyrosine kinases (RTKs) and and metabolic pathways. This points to by which the treated cells switch energy sources as a defensive response entering a quiescent like state, while activating signalling to re-activate the MAPK pathway.
HostingRepository	PRIDE
AnnounceDate	2018-07-16
AnnouncementXML	Submission_2018-07-16_05:21:33.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anna Ressa
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-14 01:28:56	ID requested
⏵ 1	2018-07-16 05:21:35	announced
2	2024-10-22 04:40:40	announced	2024-10-22: Updated project metadata.

Ressa A, Bosdriesz E, de Ligt J, Mainardi S, Maddalo G, Prahallad A, Jager M, de la Fonteijne L, Fitzpatrick M, Groten S, Altelaar AFM, Bernards R, Cuppen E, Wessels L, Heck AJR, A System-wide Approach to Monitor Responses to Synergistic BRAF and EGFR Inhibition in Colorectal Cancer Cells. Mol Cell Proteomics, 17(10):1892-1908(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: colorectal cancer, BRAF(V600E), EGFR, PTPN11, drug resistance, multi-omics, proteomics, phosphoproteomics, transcriptomics

Prof. dr. Albert J. R. Heck
contact affiliation	Biomolecular Mass Spectrometry and Proteomics Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences Utrecht University
contact email	A.J.R.Heck@uu.nl
lab head
Anna Ressa
contact affiliation	Utrecht University
contact email	a.ressa@uu.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/2018/07/PXD007740

PRIDE project URI

• PRIDE
  1. PXD007740
     1. Label: PRIDE project
     2. Name: A system-wide approach to monitor responses to synergistic BRAF and EGFR inhibition in colorectal cancer cells