PXD038378-1

PXD038378 is an original dataset announced via ProteomeXchange.

Title	Targeting an RNA polymerase II-associated PHF5A protein subcomplex with a KMT2A-WDR5 inhibitor impairs self-renewal and tumorigenicity of pancreatic cancer stem cells
Description	Pancreatic 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.
HostingRepository	PRIDE
AnnounceDate	2023-08-23
AnnouncementXML	Submission_2023-08-23_04:06:44.991.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SiweiDeng
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Dionex instrument model

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-26 03:46:39	ID requested
⏵ 1	2023-08-23 04:06:45	announced

Dataset with its publication pending

submitter keyword: epigenetics, cancer stem cells,Pancreatic cancer, PHF5A complex, KMT2A-WDR5 inhibitor

SiimPauklin
contact affiliation	Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK
contact email	siim.pauklin@ndorms.ox.ac.uk
lab head
SiweiDeng
contact affiliation	Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford
contact email	siwei.deng@hotmail.com
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD038378

PRIDE project URI

• PRIDE
  1. PXD038378
     1. Label: PRIDE project
     2. Name: Targeting an RNA polymerase II-associated PHF5A protein subcomplex with a KMT2A-WDR5 inhibitor impairs self-renewal and tumorigenicity of pancreatic cancer stem cells