PXD060790

PXD060790 is an original dataset announced via ProteomeXchange.

Title	Genome-wide in vivo CRISPR activation screen identifies BACE1 as a therapeutic vulnerability of lung cancer brain metastasis
Description	Brain metastasis occurs in up to 40% of patients with non-small cell lung cancer (NSCLC). Considerable genomic heterogeneity exists between the primary lung tumor and respective brain metastasis; however, the identity of the genes capable of driving brain metastasis is incompletely understood. Here, we carried out an in vivo genome-wide CRISPR activation (CRISPRa) screen to identify molecular drivers of brain metastasis from an orthotopic NSCLC patient-derived xenograft model. We discovered activating expression of the Alzheimer’s disease associated b-site amyloid precursor protein cleaving enzyme 1 (BACE1) led to a significant increase in brain metastasis. Furthermore, genetic and pharmacological inhibition of BACE1 blocked NSCLC brain metastasis. Mechanistically, we identified BACE1 acts through its novel substrate EGFR to drive this metastatic phenotype. Together, our data highlights the power of in vivo CRISPR screening to unveil novel molecular drivers and potential therapeutic targets of NSCLC brain metastasis.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-24_16:08:53.483.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Daniel Young
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-13 15:56:14	ID requested
⏵ 1	2025-08-24 16:08:54	announced

10.1126/scitranslmed.adu2459;

Chafe SC, Zhai K, Aghaei N, Miletic P, Huang Z, Brown KR, Mobilio D, Young D, Suk Y, Grewal S, McKenna D, Alizada Z, Kieliszek AM, Lam FC, Escudero L, Huang Q, Huebner A, Lu J, Ang P, Anand A, Custers S, Apel E, Slassi S, Brakel B, Kim J, Liu JKC, Bassey-Archibong BI, Abdo R, Shargall Y, Lu JQ, Cutz JC, Zhang Q, Li SS, Venugopal C, Hynds RE, Dufour A, Moffat J, Swanton C, Bao S, Singh SK, A genome-wide in vivo CRISPR activation screen identifies BACE1 as a therapeutic vulnerability of lung cancer brain metastasis. Sci Transl Med, 17(805):eadu2459(2025) [pubmed]

submitter keyword: BACE1, EGFR

Antoine Dufour
contact affiliation	1Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada 2 Snyder Institute for Chronic Diseases, Hotchkiss Brain Institute and McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
contact email	Antoine.dufour@ucalgary.ca
lab head
Daniel Young
contact affiliation	University of Calgary
contact email	daniel.young1@ucalgary.ca
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/2025/08/PXD060790

PRIDE project URI

• PRIDE
  1. PXD060790
     1. Label: PRIDE project
     2. Name: Genome-wide in vivo CRISPR activation screen identifies BACE1 as a therapeutic vulnerability of lung cancer brain metastasis