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PXD024521-1

PXD024521 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting Pancreatic Cancer by TAK-981, a SUMOylation Inhibitor that Activates the Immune System and Blocks Tumor Cell Cycle Progression
DescriptionThe 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) is lower than 8%. PDAC has the characteristics of high-density stroma and a distinctive immunosuppressive microenvironment and is profoundly resistant to all forms of chemo and immunotherapy. SUMOylation is a reversible post-translational modification required for cell cycle progression. We found that SUMOylation is increased in PDAC patient samples compared to primary pancreatic tissue. TAK-981, a novel highly selective and potent small molecule inhibitor of the SUMO activation enzyme E1 (SAE), selectively decreased SUMOylation in PDAC cells at the nanomolar range, thereby causing a G2/M cell cycle arrest, mitotic failure and chromosomal segregation defects. In vivo TAK-981 efficiently limited the tumor burden in the KPC3 syngeneic mouse model without evidence of general toxicity. Interestingly, we found that TAK-981 modulates the immune system, up-regulating CD8+ T cells, NK cells and down-regulating B cells in peripheral blood, spleen, lymph nodes. Treatment of mouse primary T cells ex vivo with TAK-981 activated STAT1, the key transcription factor induced by interferon signaling. Our findings indicate that inhibition of the SUMO pathway might be a potential clinical strategy to target PDAC by inhibiting tumor cell division and activating anti-tumor immunity.
HostingRepositoryPRIDE
AnnounceDate2022-01-10
AnnouncementXMLSubmission_2022-01-10_11:28:42.777.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRomán González-Prieto
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-03-04 03:58:20ID requested
12022-01-10 11:28:43announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: SUMO, Pancreatic Cancer, TAK-981
Contact List
Alfred C.O. Vertegaal
contact affiliationCell and Chemical Biology Leiden University Medical Center (LUMC) The Netherlands
contact emailvertegaal@lumc.nl
lab head
Román González-Prieto
contact affiliationLeiden University Medical Center (LUMC)
contact emailR.Gonzalez_Prieto@lumc.nl
dataset submitter
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Dataset FTP location
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