PXD054102-1

PXD054102 is an original dataset announced via ProteomeXchange.

Title	Disruption of basal cell identity by Rank signaling drives mammary tumorigenesis
Description	Rank signaling regulates mammary gland development and epithelial cell differentiation. Rank receptor is expressed by mammary basal and luminal populations, but, unlike luminal Rank, the contribution of basal Rank signaling to MG homeostasis remains poorly studied. We have combined timely regulated basal specific Rank expression with lineage tracing models and unveiled that basal Rank signaling controls basal cell identity in postnatal mammary glands. Ectopic basal Rank disrupts basal but also luminal cell identity, resulting in aberrant luminal-like differentiation of basal cells and impaired lactogenesis. Mechanistically, overactivation of basal Rank signaling leads to basal cell lineage infidelity, illustrated by the appearance of premalignant lesions composed by a basal-derived hybrid population with alveolar features which ultimately generates basal and luminal breast adenocarcinomas. Proteomic, transcriptomic and chromatin analyses support that the loss of tumor suppressive epigenetic regulators driven by basal Rank contributes to epithelial cell dedifferentiation and tumorigenesis. The basal Rank signature generated associates to poor prognosis particularly in human adenocarcinomas of the luminal subtype stressing the clinical relevance of our findings. Interestingly, our results reinforce the idea that luminal breast tumors might originate from basal cells that have suffered a luminal-like aberrant dedifferentiation triggered by Rank signaling.
HostingRepository	PRIDE
AnnounceDate	2026-02-02
AnnouncementXML	Submission_2026-02-02_14:29:21.432.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pilar Ximenez-Embun
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-22 02:58:33	ID requested
⏵ 1	2026-02-02 14:29:21	announced

Dataset with its publication pending

submitter keyword: breast cancer, basal cell, identity infidelity, Rank, mouse,Mammary gland

Marta Isasa
contact affiliation	Proteomics Unit Spanish National Cancer Research Center (CNIO) 28029 Madrid Spain
contact email	misasa@cnio.es
lab head
Pilar Ximenez-Embun
contact affiliation	Proteomics Group
contact email	mpximenez@cnio.es
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/2026/02/PXD054102

PRIDE project URI

• PRIDE
  1. PXD054102
     1. Label: PRIDE project
     2. Name: Disruption of basal cell identity by Rank signaling drives mammary tumorigenesis