PXD058134-1

PXD058134 is an original dataset announced via ProteomeXchange.

Title	Rank signaling drives basal cell-lineage infidelity leading to 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 that of luminal, the contribution of basal Rank signaling to mammary gland homeostasis remains poorly studied. Combining timely-regulated, basal-specific Rank expression with lineage tracing strategies we unveiled that Rank signaling controls basal cell identity in postnatal mammary glands. Enhanced basal Rank disrupts basal and luminal cell identity, resulting in aberrant luminal-like differentiation of basal cells, defective lactation and the appearance of premalignant lesions composed of a basal-derived hybrid population with luminal/alveolar features, which ultimately generates basal and luminal breast adenocarcinomas. Mechanistically, phospho-proteomic, transcriptomic and chromatin analyses support that basal Rank activation triggers the loss of tumor suppressive epigenetic regulators, leading to chromatin remodeling, disruption of basal identity and tumorigenesis. We uncover a basal Rank gene signature that can be predictive of progression from in situ to invasive adenocarcinomas and associates with poor prognosis in breast cancer patients, particularly in those diagnosed with luminal adenocarcinomas, underlining the clinical relevance of our findings. Our results reinforce the idea that basal lineage infidelity triggered by Rank signaling contribute to generation from pre-invasive lesions and transition to invasive breast cancer.
HostingRepository	PRIDE
AnnounceDate	2026-02-02
AnnouncementXML	Submission_2026-02-02_07:49:37.751.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eduardo Zarzuela
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-21 04:50:27	ID requested
⏵ 1	2026-02-02 07:49:38	announced

Dataset with its publication pending

submitter keyword: Rank signaling,phosphorylation, tumorogenesis

Marta Isasa
contact affiliation	CNIO
contact email	misasa@cnio.es
lab head
Eduardo Zarzuela
contact affiliation	Centro Nacional de Investigaciones Oncológicas
contact email	eduzarfer@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058134
     1. Label: PRIDE project
     2. Name: Rank signaling drives basal cell-lineage infidelity leading to mammary tumorigenesis