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PXD038378-1

PXD038378 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting an RNA polymerase II-associated PHF5A protein subcomplex with a KMT2A-WDR5 inhibitor impairs self-renewal and tumorigenicity of pancreatic cancer stem cells
DescriptionPancreatic cancer (PC) remains one of the most aggressive and life-threatening malignancies known for its notorious resistance to chemotherapy. This is increasingly ascribed to the subpopulation of undifferentiated cells, known as pancreatic cancer stem cells (PCSCs), which are evolutionary fitter than other tumor cells to evade the cytotoxic effects of chemotherapy. Those cells are crucial for tumor relapse as they possess ‘stem cell-like’ features of self-renewal and differentiation. However, what molecular mechanisms maintain the unique characteristics of PCSCs are poorly understood. Here, we identified an RNA polymerase II-associated PHF5A-PHF14-HMG20A-RAI1-KMT2A transcriptional subcomplex, which regulates the stemness characteristics and tumorigenicity of PCSCs through epigenetic control of gene expression. Targeting the protein subcomplex with a KMT2A-WDR5 inhibitor attenuated the self-renewal and in vivo tumorigenicity of PCSCs, thus offering a novel anti-PCSCs targeting strategy for enhancing the efficiency of chemotherapy which is likely to translate into durable clinical responses in PC patients.
HostingRepositoryPRIDE
AnnounceDate2023-08-23
AnnouncementXMLSubmission_2023-08-23_04:06:44.991.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSiweiDeng
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentDionex instrument model
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-11-26 03:46:39ID requested
12023-08-23 04:06:45announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: epigenetics, cancer stem cells,Pancreatic cancer, PHF5A complex, KMT2A-WDR5 inhibitor
Contact List
SiimPauklin
contact affiliationBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK
contact emailsiim.pauklin@ndorms.ox.ac.uk
lab head
SiweiDeng
contact affiliationNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford
contact emailsiwei.deng@hotmail.com
dataset submitter
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Dataset FTP location
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PRIDE project URI
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