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PXD021729

PXD021729 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTyrosine phosphoproteomics of patient-derived xenografts reveals ephrin type-B receptor 4 tyrosine kinase as novel therapeutic target in pancreatic cancer
DescriptionPancreatic ductal adenocarcinoma is a recalcitrant tumor with minimal response to conventional chemotherapeutic approaches. Oncogenic signaling by activated tyrosine kinases has been implicated in cancers resulting in activation of diverse effector signaling pathways. Thus, discovery of aberrantly activated tyrosine kinases is of great interest in developing novel therapeutic strategies in treatment and management of pancreatic cancer. Patient-derived tumor xenografts (PDXs) in immunodeficient mice serve as potentially valuable preclinical model as it maintain the histological and molecular heterogeneity of the progenitor human tumor. Here, we employed high resolution mass spectrometry combined with immuno-affinity purification using anti-phosphotyrosine antibodies to profile tyrosine phosphoproteome across 13 pancreatic ductal adenocarcinoma PDX models. This analysis resulted in identification of 1,219 tyrosine phosphorylated sites mapping on 724 proteins. The mass spectrometric analysis revealed widespread and heterogeneous activation of both receptor and non-receptor tyrosine kinases. Studies carried out in mice confirmed ephrin type-B receptor 4 (EphB4) as a potential therapeutic target based on the efficacy of human serum albumin-conjugated soluble EphB4 in mice bearing orthotopic xenografts. In summary, we present the comprehensive landscape of tyrosine phosphoproteome with EphB4 as a promising therapeutic target in pancreatic ductal adenocarcinoma.
HostingRepositoryPRIDE
AnnounceDate2021-05-24
AnnouncementXMLSubmission_2021-05-24_11:46:07.193.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAkhilesh Pandey
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-28 23:31:42ID requested
12021-05-24 11:46:07announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Cancer, PDX, receptor tyrosine kinase, signaling, pTyr
Contact List
Akhilesh Pandey
contact affiliationDepartment of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN 55905 USA
contact emailpandey.akhilesh@mayo.edu
lab head
Akhilesh Pandey
contact affiliationDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905
contact emailpandey.akhilesh@mayo.edu
dataset submitter
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