PXD062969

PXD062969 is an original dataset announced via ProteomeXchange.

Title	Nucleophosmin sustains WNT-driven cell proliferation and tumour initiation in vivo
Description	Nucleophosmin (NPM1) is a nucleolar protein frequently mutated in haematopoietic malignancies and overexpressed in many solid tumours, but little is known about its functional role in carcinogenesis. Here, we identify NPM1 as a commonly upregulated gene following APC loss in tissues that positively respond to high WNT signalling. High NPM1 expression correlates with increased proliferation in patients with colorectal cancer (CRC). We show that whilst dispensable for adult epithelial tissue homeostasis, NPM1 loss has a profound effect on WNT-driven intestinal and liver tumourigenesis, leading to reduced proliferation and extension of survival. Mechanistically, NPM1 depletion triggers integrated stress response (ISR) and p53 pathway activation. Genetically or chemically blunting these pathways, rescues proliferation following NPM1 loss. Overall, our results demonstrate that NPM1 supports WNT-driven cell proliferation and tumour initiation by attenuating induction of ISR and p53 pathway activation. Being dispensable for homeostasis, NPM1 presents itself as a promising target for cancer therapy in WNT-driven tumours with functional p53, including treatment-refractory KRAS-mutant CRC and hepatic cancers.
HostingRepository	PRIDE
AnnounceDate	2025-08-12
AnnouncementXML	Submission_2025-08-12_04:05:14.812.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD062969
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sergio Lilla
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-15 03:08:51	ID requested
⏵ 1	2025-08-12 04:05:15	announced

10.6019/PXD062969;

submitter keyword: Nucleophosmin, WNT signalling, TMT16plex, colorectal cancer

Martin Bushell
contact affiliation	Cancer Research UK Scotland Institute (Formerly the Cancer Research UK Beatson Institute) Garscube Estate Switchback Road Bearsden Glasgow, G61 1BD
contact email	Martin.Bushell@glasgow.ac.uk
lab head
Sergio Lilla
contact affiliation	Proteomics
contact email	s.lilla@beatson.gla.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062969
     1. Label: PRIDE project
     2. Name: Nucleophosmin sustains WNT-driven cell proliferation and tumour initiation in vivo