PXD048201
PXD048201 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | DYRK1B blockade promotes tumoricidal macrophage activity in pancreatic cancer |
Description | Highly 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. |
HostingRepository | MassIVE |
AnnounceDate | 2024-06-05 |
AnnouncementXML | Submission_2024-06-05_06:55:11.882.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Johannes Graumann |
SpeciesList | scientific name: Mus musculus; |
ModificationList | unknown modification; unknown modification |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2024-01-02 04:06:07 | ID requested | |
⏵ 1 | 2024-06-05 06:55:12 | announced |
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 affiliation | Philipps University Marburg |
contact email | lauth@staff.uni-marburg.de |
lab head | |
Johannes Graumann | |
contact affiliation | Philipps-University Marburg |
contact email | johannes.graumann@uni-marburg.de |
dataset submitter |
Full Dataset Link List
MassIVE dataset URI |
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://massive.ucsd.edu/v06/MSV000093747/ |