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PXD048201

PXD048201 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDYRK1B blockade promotes tumoricidal macrophage activity in pancreatic cancer
DescriptionHighly malignant pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant immunosuppressive and fibrotic tumor microenvironment (TME). Future therapeutic attempts therefore demand targeting of both compartments in order to be effective. We show here that Dual Specificity and Tyrosine Phosphorylation-regulated Kinase 1B (DYRK1B) represents a compartment-agnostic anti-cancer target in PDAC. DYRK1B is mainly expressed by pancreatic epithelial cancer cells and modulates the influx and activity of TME-associated macrophages through effects on the cancer cells themselves as well as affecting the tumor secretome. Mechanistically, genetic ablation or pharmacological inhibition of DYRK1B strongly attracts tumoricidal macrophages and in addition downregulates the phagocytosis checkpoint and "don't eat me"-signal CD24 on cancer cells, resulting in enhanced tumor cell phagocytosis. Consequently, tumor cells lacking DYRK1B hardly expand in transplantation experiments despite doing so rapidly in culture. Furthermore, combining a small-molecule DYRK1B-directed therapy with mTOR inhibition and conventional chemotherapy stalls the growth of established tumors and results in significant extension of life span in a highly aggressive autochthonous model of PDAC. In light of DYRK inhibitors currently entering clinical phase testing, our data thus provide a novel and clinically translatable approach targeting the cancer cell compartment and its microenvironment, both.
HostingRepositoryMassIVE
AnnounceDate2024-06-05
AnnouncementXMLSubmission_2024-06-05_06:55:11.882.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJohannes Graumann
SpeciesList scientific name: Mus musculus;
ModificationListunknown modification; unknown modification
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-01-02 04:06:07ID requested
12024-06-05 06:55:12announced
Publication List
Brichkina A, Ems M, Suezov R, Singh R, Lutz V, Picard FSR, Nist A, Stiewe T, Graumann J, Daude M, Diederich WE, Finkernagel F, Chung HR, Bartsch DK, Roth K, Keber C, Denkert C, Huber M, Gress TM, Lauth M, DYRK1B blockade promotes tumoricidal macrophage activity in pancreatic cancer. Gut, 73(10):1684-1701(2024) [pubmed]
Keyword List
submitter keyword: pancreatic ductal adenocarcinoma (PDAC), Tyrosine Phosphorylation-regulated Kinase 1B (DYRK1B)
Contact List
Matthias Lauth
contact affiliationPhilipps University Marburg
contact emaillauth@staff.uni-marburg.de
lab head
Johannes Graumann
contact affiliationPhilipps-University Marburg
contact emailjohannes.graumann@uni-marburg.de
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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