PXD049279-2

PXD049279 is an original dataset announced via ProteomeXchange.

Title	A common human PCSK9 germline variant drives breast cancer metastasis via the LRP1 receptor
Description	Identifying patients at risk for metastatic relapse is a critical need in oncology. We identified a common missense germline variant in PCSK9 (rs562556) that associates with reduced breast cancer survival outcomes in multiple cohorts. Genetic modeling of this gain-of-function single nucleotide variant in mice revealed that it causally promoted breast cancer metastasis. Conversely, host PCSK9 deletion reduced metastatic colonization in multiple breast cancer models. Host PCSK9 promoted metastatic initiation events in lung and increased proliferative competence by targeting tumoral LRP1 receptors which repress metastasis-promoting genes. Antibody-mediated therapeutic inhibition of PCSK9 suppressed breast cancer metastasis in multiple models. rs562556 stratified women in a large Swedish early-stage breast cancer cohort into those with 98% versus 78% distant-metastasis-free interval at 15 years after diagnosis. Our findings reveal that a commonly inherited genetic alteration predicts breast cancer survival and governs breast cancer metastasis—uncovering a hereditary basis underlying a prevalent cause of mortality.
HostingRepository	PRIDE
AnnounceDate	2024-12-12
AnnouncementXML	Submission_2024-12-11_21:36:35.251.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Soren Heissel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-08 08:30:53	ID requested
1	2024-12-05 06:37:53	announced
⏵ 2	2024-12-11 21:36:35	announced	2024-12-12: Updated project metadata.

10.1016/J.CELL.2024.11.009;

submitter keyword: breast cancer

PCSK9

Sohail F Tavazoie
contact affiliation	Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY, USA
contact email	sohail.tavazoie@rockefeller.edu
lab head
Soren Heissel
contact affiliation	Research Support Specialist
contact email	sheissel@rockefeller.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/2024/12/PXD049279

PRIDE project URI

• PRIDE
  1. PXD049279
     1. Label: PRIDE project
     2. Name: A common human PCSK9 germline variant drives breast cancer metastasis via the LRP1 receptor