PXD022072

PXD022072 is an original dataset announced via ProteomeXchange.

Title	Proteomics uncover EPHA2 in cetuximab resistant colorectal cancer cell lines as a potential novel therapeutic target
Description	In metastatic colorectal cancer (mCRC), primary and acquired resistance against anti-EGFR targeted monoclonal antibodies, such as cetuximab (CET), were shown to be frequently caused by activating alterations in RAS genes (KRAS or NRAS). To this day no efficient second-line treatment options have emerged to treat mCRC upon emergence of acquired KRAS alterations. In order to uncover potential targets for second-line targeted therapies, we used mass spectrometric proteomics to shed light on kinome reprogramming in an established model of acquired, KRAS associated CET resistance. This CET resistance was reflected by significant changes in the kinome, most of them individual to each cell line. Interestingly a common theme in all investigated resistant cell lines was the upregulation of the Ephrin type-A receptor 2 (EPHA2), a well-known driver of cell migration. Expectedly resistant cell lines displayed increased migration (p<0.01) that was significantly reduced by targeting the EPHA2 signalling axis using RNA interference (p<0.001), ephrin-A1 stimulation (p<0.001), dasatinib (p<0.01) or anti-EPHA2 antibody treatment (p<0.001), identifying it as an actionable target in CET resistant mCRC. These results highlight EPHA2 and its role in KRAS mutated acquired CET resistance in mCRC and identify it as a potential target for the development of future precision medicine therapies.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:15:32.335.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anna Jarzab
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-19 05:17:48	ID requested
1	2023-03-10 19:08:41	announced
⏵ 2	2023-11-14 08:15:33	announced	2023-11-14: Updated project metadata.

Torlot L, Jarzab A, Albert J, P, ó, k-Udvari Á, Stahler A, Holch JW, Gerlinger M, Heinemann V, Klauschen F, Kirchner T, Kumbrink J, K, ü, ster B, Jung A, Proteomics uncover EPHA2 as a potential novel therapeutic target in colorectal cancer cell lines with acquired cetuximab resistance. J Cancer Res Clin Oncol, 149(2):669-682(2023) [pubmed]

submitter keyword: EPHA2, cetuximab resistance,Proteomics

Bernhard Kuster
contact affiliation	Chair of Proteomics and Bioanalytics Technical University of Munich Germany
contact email	kuster@tum.de
lab head
Anna Jarzab
contact affiliation	Technical University of Munich
contact email	anna.jarzab@tum.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/2023/03/PXD022072

PRIDE project URI

• PRIDE
  1. PXD022072
     1. Label: PRIDE project
     2. Name: Proteomics uncover EPHA2 in cetuximab resistant colorectal cancer cell lines as a potential novel therapeutic target