PXD060027-1

PXD060027 is an original dataset announced via ProteomeXchange.

Title	Targeting Fibrillarin-mediated ribosomal RNA maturation as a novel therapeutic vulnerability in triple-negative breast cancer
Description	Triple-negative breast cancer (TNBC) is among the most challenging breast cancer subtypes to treat due to the lack of effective therapeutic options. Ribosome biogenesis has recently emerged as a promising therapeutic target across various cancers. Current ribosome biogenesis inhibitors primarily target ribosomal RNA (rRNA) synthesis through RNA polymerase I (RNA Pol I) inhibition. However, ribosome biogenesis also depends on a variety of rRNA maturation factors, many of which are essential for ribosome assembly. It remains unclear whether ribosome biogenesis and its maturation factors represent therapeutic vulnerabilities in TNBC. Here, we demonstrate that ribosome biogenesis-related genes are notably overexpressed in TNBC compared to other breast cancer subtypes, highlighting its critical role in TNBC progression. Accordingly, we show that RNA Pol I inhibition exerts potent anti-proliferative effects in pre-clinical models of TNBC, both in vitro and in vivo. However, the DNA-damaging activity of RNA Pol I inhibitors raises safety concerns, highlighting the need for alternative strategies to inhibit ribosome biogenesis. To this end, we show that targeting a downstream rRNA maturation step, specifically pre-rRNA cleavage, by inhibiting the maturation factor Fibrillarin, also inhibits tumor growth in TNBC models. Notably, ribosome biogenesis inhibition—through either RNA Pol I or Fibrillarin targeting—induces cell cycle arrest without triggering significant cell death. These findings establish ribosome biogenesis as a therapeutic vulnerability in TNBC and identify rRNA maturation, and Fibrillarin in particular, as novel targets for potential therapeutic intervention.
HostingRepository	PRIDE
AnnounceDate	2025-11-25
AnnouncementXML	Submission_2025-11-25_06:13:30.815.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Carine Froment
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-21 10:10:23	ID requested
⏵ 1	2025-11-25 06:13:31	announced

10.1186/s13058-025-02163-x;

Jouines C, Lo Monaco P, Gaucherot A, Radermecker J, Isaac C, Bourdelais F, Monet MA, Meyer M, Chalabi-Dchar M, Nguyen Van Long F, Baillon L, Froment C, Marcoux J, Vanbelle C, Fenouil T, Durand S, Giraud S, Diaz JJ, Marcel V, Catez F, Fibrillarin-mediated ribosomal RNA maturation is a novel therapeutic vulnerability in triple-negative breast cancer. Breast Cancer Res, 27(1):202(2025) [pubmed]

submitter keyword: Label-free quantitative proteomics, targeting ribosome biogenesis, nanoLC-MS/MS,Triple-negative breast cancer

Frédéric Catez
contact affiliation	Ribosome, Traduction and Cancer team, LabEx DEVweCAN, Institut Convergence Plascan, LyriCAN+, Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, 69008 Lyon, France.
contact email	frederic.catez@lyon.unicancer.fr
lab head
Carine Froment
contact affiliation	IPBS-CNRS
contact email	carine.froment@ipbs.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060027
     1. Label: PRIDE project
     2. Name: Targeting Fibrillarin-mediated ribosomal RNA maturation as a novel therapeutic vulnerability in triple-negative breast cancer