PXD041042

PXD041042 is an original dataset announced via ProteomeXchange.

Title	Protein Kinase D drives the secretion of invasion mediators in triple negative breast cancer cell lines
Description	Protein kinase D (PKD) regulates protein secretion at the Golgi complex and has been found to have a pro-oncogenic role in triple-negative breast cancer (TNBC). PKD was previously reported to regulate the secretion of tumor-promoting factors in prostate and pancreatic cancer. Whether PKD plays a similar role in TNBC remains unknown. Here, we used mass spectrometry-based proteomics to characterize the secreted proteome collected from the TNBC cell lines MDA-MB-231 and MDA-MB-468 following pharmacological PKD2 and PKD3 inhibition. Analysis of secretome signatures of response revealed several extracellular matrix related proteins decreased upon PKD inhibition. Amongst the downregulated proteins were previously described TNBC invasion mediators, such as TNC, STC-1, LIF, MMP-1 and M-CSF. The secretion of these proteins, as well as of MMP-13, IL-11 and GM-CSF, was further validated by multiplex assays to be regulated by PKD. Secretion regulation of this protein set by PKD was more evident in TNBC metastatic cell lines than in primary tumor-derived. Individual knockdown of PKD2 and PKD3 revealed that secretion of this protein set is predominantly PKD2-driven in MDA-MB-231 cells. This study improves the current understanding of PKD’s contribution to TNBC secretion and uncovers a novel function of PKD2 in the release of a pro-invasive secretome. / This study improves the current understanding of PKD’s contribution to TNBC secretion and uncovers the distinct pro-invasive substrates of PKD2 and PKD3.
HostingRepository	PRIDE
AnnounceDate	2024-01-17
AnnouncementXML	Submission_2024-01-17_06:26:11.781.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thang Pham
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-23 03:51:48	ID requested
⏵ 1	2024-01-17 06:26:12	announced

10.1016/J.ISCI.2024.108958;

submitter keyword: secretion, proteomics, cytokine, invasion,TNBC, protein kinase D, tumor microenvironment, extracellular matrix, metastasis

Connie Jimenez
contact affiliation	Amsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology, Cancer Center Amsterdam, OncoProteomics Laboratory, Amsterdam, Netherlands
contact email	c.jimenez@amsterdamumc.nl
lab head
Thang Pham
contact affiliation	Amsterdam UMC
contact email	t.pham@amsterdamumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041042
     1. Label: PRIDE project
     2. Name: Protein Kinase D drives the secretion of invasion mediators in triple negative breast cancer cell lines