PXD021729-1

PXD021729 is an original dataset announced via ProteomeXchange.

Title	Tyrosine phosphoproteomics of patient-derived xenografts reveals ephrin type-B receptor 4 tyrosine kinase as novel therapeutic target in pancreatic cancer
Description	Pancreatic 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.
HostingRepository	PRIDE
AnnounceDate	2021-05-24
AnnouncementXML	Submission_2021-05-24_11:46:07.193.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Akhilesh Pandey
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-28 23:31:42	ID requested
⏵ 1	2021-05-24 11:46:07	announced

Dataset with its publication pending

submitter keyword: Cancer, PDX, receptor tyrosine kinase, signaling, pTyr

Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN 55905 USA
contact email	pandey.akhilesh@mayo.edu
lab head
Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905
contact email	pandey.akhilesh@mayo.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021729
     1. Label: PRIDE project
     2. Name: Tyrosine phosphoproteomics of patient-derived xenografts reveals ephrin type-B receptor 4 tyrosine kinase as novel therapeutic target in pancreatic cancer