PXD046652-1

PXD046652 is an original dataset announced via ProteomeXchange.

Title	FOXA1 proximity labeling reveals novel interactions with NR2C2 in ER+ breast cancer
Description	Approximately 75% of breast cancers are driven by the estrogen receptor alpha (ER), and despite the advent of endocrine therapy to block ER signaling pathways, a significant portion of women develop resistance to these drugs. The pioneer factor FOXA1 has been shown to facilitate nearly all DNA-binding events of ER in response to estrogen in ER+ breast cancer (ER+BC). Notably, up-regulation of FOXA1 is a hallmark of endocrine-resistant phenotypes and has been shown to reprogram enhancer elements, leading to an altered transcriptome. However, FOXA1 is a critical pioneer factor for multiple nuclear hormone receptors aside from ER and is implicated in regulation of important factors such as HER2 and the androgen receptor (AR). With the diverse array of breast cancer molecular subtypes displaying complex interplay between ER, HER2, AR, PR, and other hormone receptors, describing the complete ensemble of FOXA1 binding partners in various contexts, such as endocrine-resistant tumors, is of increasing importance. To classify FOXA1 interactors, we generated MCF-7 cell lines stably expressing the biotin ligase miniTurbo fused to the N- or C-terminus of FOXA1. Using proximity labeling (PL) coupled with LC-MS/MS, we have comprehensively cataloged interactors of FOXA1, including expected proteins such as ER, AR, MLL3, YAP1, and GATA-3. Moreover, we have discovered 157 previously unpublished interactors of FOXA1. Importantly, poorer prognosis for relapse-free survival among ER+BC patients is associated with several of these novel interactors, including NR2C2, an orphan nuclear receptor previously shown to regulate various nuclear hormone receptor signaling but whose roles in breast cancer remain unclear. NR2C2 ChIP-seq in MCF-7 cells under control or FOXA1-depleted conditions revealed multiple NR2C2 binding mechanisms in relation to FOXA1 levels and binding, suggesting possible coordinate regulation of key loci. Integrating proteomic and genomic approaches, we have potentially highlighted new mechanisms of FOXA1 that could have future clinical impacts.
HostingRepository	PRIDE
AnnounceDate	2025-10-06
AnnouncementXML	Submission_2025-10-05_16:42:36.368.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christine Mills
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-03 09:58:38	ID requested
⏵ 1	2025-10-05 16:42:37	announced

Plagens RN, Tirado CSR, Li S, Maldonado-Vazquez N, Montes-Rodriguez IM, Dutil J, Mills CA, Herring LE, Franco HL, Mapping the FOXA1 Interactome in ER+ Breast Cancer Cells using Proximity Labeling Reveals Novel Interactions with the Orphan Nuclear Receptor NR2C2. Mol Cancer Res, ():(2025) [pubmed]

10.1158/1541-7786.mcr-25-0085;

submitter keyword: NR2C2, biotin ligase, FOXA1, proximity labeling,breast cancer

Hector Franco
contact affiliation	Lineberger Comprehensive Cancer Center Department of Genetics UNC Chapel Hill School of Medicine 125 Mason Farm Rd Chapel Hill, NC 27599
contact email	hfranco@med.unc.edu
lab head
Christine Mills
contact affiliation	University of North Carolina - Chapel Hill
contact email	allie.mills@unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046652
     1. Label: PRIDE project
     2. Name: FOXA1 proximity labeling reveals novel interactions with NR2C2 in ER+ breast cancer