PXD057102-1

PXD057102 is an original dataset announced via ProteomeXchange.

Title	IKKα modulates colorectal cancer metastasis by counteracting tight junction stabilization and collective cell migration.
Description	The IKK kinase was previously found to activate multiple oncogenic and therapy-resistance pathways, including ATM/DDR, BRD4, and JAK/STAT3, independently of canonical NF-B signaling. Here, we show that suppression of IKK, either genetically or pharmacologically, imposes a pro-metastatic activity on colorectal cancer (CRC) patient-derived organoid (PDO) cells, which is linked to an increase in the protein levels of the tight junction protein ZO-1 and CLDN2, and a shift in their migratory mode towards collective migration. Analysis of single-cell (sc)RNA-seq data revealed an accumulation of the tight junction signature in the metastatic populations. Specifically, PDO cells contain three distinct epithelial cell clusters (C2, C4 and C8) with concomitant enrichment of the tight junction and metastasis-associated EpiHR signatures, whose unique genetic signatures are upregulated upon depletion of IKK and enriched in PDO-derived metastases. CLDN2 inhibition or depletion abolishes the metastatic activity of IKK KO PDO cells in vivo. By analyzing human paraffin-embedded CRC specimens, we have detected the presence of vascular tumor infiltrates with cluster-like or glandular phenotypes and high levels of ZO-1 and CLDN2-positive junctions. Collectively, our results suggest that high levels of tight junction proteins in CRC cells impose a pro-metastatic collective CRC cell migration, which can be detected in the vascular infiltrates at diagnosis. We propose that after validation, this type of exploration could be standardized in clinical routine and CLDN2 and the elements defining tight junction-enriched tumor clusters could be considered as metastasis biomarkers and candidate therapeutic target for CRC.
HostingRepository	PRIDE
AnnounceDate	2025-12-01
AnnouncementXML	Submission_2025-12-01_13:30:01.891.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kieran Wynne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-23 06:12:21	ID requested
⏵ 1	2025-12-01 13:30:02	announced

Dataset with its publication pending

submitter keyword: IKKα, cell migration., colorectal cancer, metastasis

Prof Lluís Espinosa
contact affiliation	1Cancer Research Program, Hospital del Mar Research Institute, Doctor Aiguader 88, Barcelona 08003, Spain. Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.
contact email	lespinosa@researchmar.net
lab head
Kieran Wynne
contact affiliation	University College Dublin
contact email	kieran.wynne1@ucd.ie
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057102
     1. Label: PRIDE project
     2. Name: IKKα modulates colorectal cancer metastasis by counteracting tight junction stabilization and collective cell migration.