PXD049187-1

PXD049187 is an original dataset announced via ProteomeXchange.

Title	DAPK3 modulates migration and invasion of triple negative breast cancers
Description	A mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was applied to analyze 16 patient-derived xenografts (PDXs) leading to the discovery that Death-Associated Protein Kinase 3 (DAPK3) is significantly and specifically overexpressed in triple negative breast cancer (TNBC). Validation studies confirmed the enrichment of DAPK3 at the protein level, independent of RNA expression, in both TNBC cell lines and tumors. Genomic knockout of DAPK3 in TNBC cell lines inhibited in vitro migration and invasion, along with downregulation of an epithelial-mesenchymal transition (EMT) signature. The kinase and leucine-zipper domains within DAPK3 were shown by mutational analysis to be essential for functionality. Notably, DAPK3 was found to inhibit the levels of desmoplakin (DSP), a crucial component of the desmosome complex, thereby explaining TNBC migration and invasion effects. Further exploration with immunoprecipitation-mass spectrometry (IP-MS) identified Leucine-zipper protein 1 (LUZP1) as a strong binding partner of DAPK3, engaging in a leucine-zipper-domain-mediated interaction that protects DAPK3 from degradation. Thus, DAPK3 emerges as a novel regulator of EMT components in TNBC.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_12:54:45.690.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthew Holt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-05 11:24:25	ID requested
⏵ 1	2025-05-06 12:54:46	announced

Wang J, Tran-Huynh AM, Kim BJ, Chan DW, Holt MV, Fandino D, Yu X, Qi X, Wang J, Zhang W, Wu YH, Anurag M, Zhang XHF, Zhang B, Cheng C, Foulds CE, Ellis MJ, Death-associated protein kinase 3 modulates migration and invasion of triple-negative breast cancer cells. PNAS Nexus, 3(9):pgae401(2024) [pubmed]

10.1093/pnasnexus/pgae401;

submitter keyword: LUZP1, EMT, Breast Cancer, Cancer,DAPK3, PDX

Matthew V Holt
contact affiliation	1Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
contact email	mvholt@bcm.edu
lab head
Matthew Holt
contact affiliation	BCM
contact email	mvholt@bcm.edu
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/2025/05/PXD049187

PRIDE project URI

• PRIDE
  1. PXD049187
     1. Label: PRIDE project
     2. Name: DAPK3 modulates migration and invasion of triple negative breast cancers