PXD008582

PXD008582 is an original dataset announced via ProteomeXchange.

Title	In vitro DDR1 signalling
Description	The clinical management of metastatic colorectal cancer (mCRC) faces major challenges. For instance, patients harbouring oncogenic mutations in RAS signalling do not respond to anti-EGFR targeted treatment. Therefore, RAS-independent therapies are needed. Interestingly nilotinib, a clinically approved drug for chronic myeloid leukaemia, inhibits human CRC cell invasion in vitro and reduces their metastatic potential in intrasplenic tumour mouse models. Nilotinib acts by inhibiting the kinase activity of DDR1, a receptor tyrosine kinase for collagens, which we identified as a RAS-independent inducer of CRC metastasis. Using quantitative phosphoproteomics, we identified BCR as a new DDR1 substrate and demonstrated that nilotinib prevents DDR1-mediated BCR phosphorylation on Tyr177, which is important for maintaining -catenin transcriptional activity necessary for tumour cell invasion. DDR1 kinase inhibition also reduced the invasion of patient-derived metastatic and circulating CRC cell lines.
HostingRepository	PRIDE
AnnounceDate	2018-01-31
AnnouncementXML	Submission_2018-02-16_05:49:49.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Debora Bonenfant
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-02 23:43:28	ID requested
1	2018-01-31 00:52:33	announced
⏵ 2	2018-02-16 05:49:50	announced	Updated publication reference for PubMed record(s): 29438985.

Jeitany M, Leroy C, Tosti P, Lafitte M, Le Guet J, Simon V, Bonenfant D, Robert B, Grillet F, Mollevi C, El Messaoudi S, Otandault A, Canterel-Thouennon L, Busson M, Thierry AR, Martineau P, Pannequin J, Roche S, Sirvent A, new therapeutic strategy for metastatic colorectal cancer. EMBO Mol Med, 10(4):(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: metastatic colorectal cancer, signalling, DDR1 tyrosine kinase,

Debora Bonenfant, Novartis Institutes for BioMedical Research
contact affiliation	Debora Bonenfant, Novartis Institutes for BioMedical Research, Basel, Switzerland
contact email	debora.bonenfant@novartis.com
lab head
Debora Bonenfant
contact affiliation	Novartis Institutes for BioMedical Research
contact email	debora.bonenfant@novartis.com
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/2018/01/PXD008582

PRIDE project URI

• PRIDE
  1. PXD008582
     1. Label: PRIDE project
     2. Name: In vitro DDR1 signalling