PXD053649-1

PXD053649 is an original dataset announced via ProteomeXchange.

Title	Spatial proteomics reveals distinct protein patterns in a lissencephaly-like cortical migration disorder caused by LIN28A overexpression and WNT activation
Description	Developmental signalling pathways act in stage and tissue dependent relation and mis-activation can drive tumour formation. The RNA-binding protein LIN28A maintains stemness and is overexpressed in embryonal brain tumours. Activating mutations of CTNNB1 - the WNT pathway effector - have been reported in respective brain tumours. The aim of this study was to investigate the interplay of these oncogenic proteins during embryonal brain development. The combination of both oncogenic factors did not lead to brain tumour formation but resulted in disturbed lamination and impaired cell migration in the cerebral cortex. Spatially resolved proteome analysis revealed imbalances of the extracellular matrix protein LAMB1 and its receptors RPSA and ITGB1 accompanied by a porous pial border and overmigration of neural cells. Cajal-Retzius cells were misplaced in deeper cortex regions without affecting general REELIN levels and additional reduced levels of a-DYSTROGLYCAN. Taken together, the interplay of LIN28A and CTNNB1 resulted in a cortical migration disorder showing histomorphological and molecular similarities to human Cobblestone lissencephaly (type 2), highlighting novel implications of the oncogene LIN28A in extracellular matrix integrity.
HostingRepository	PRIDE
AnnounceDate	2025-09-15
AnnouncementXML	Submission_2025-09-14_22:58:52.045.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Manuela Moritz
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-04 18:03:11	ID requested
⏵ 1	2025-09-14 22:58:53	announced

Navoli, ć J, Hawass S, Moritz M, Hahn J, Middelkamp M, Gocke A, Dottermusch M, Schumann Y, Ruck L, Krisp C, Godbole S, Sumislawski P, K, ö, ppen N, Gargioni E, Schl, ü, ter H, Neumann JE, Spatial Proteomics Reveals Distinct Protein Patterns in Cortical Migration Disorders Caused by LIN28A Overexpression and WNT Activation. Mol Cell Proteomics, 24(9):101037(2025) [pubmed]

10.1016/j.mcpro.2025.101037;

submitter keyword: cortical migration disorder, CTNNB1,Spatial proteomics, LIN28A

Hartmut Schlüter
contact affiliation	Section/Core Facility Mass Spectrometry and Proteomics, Center for Diagnostics, University Medical Center Hamburg−Eppendorf
contact email	hschluet@uke.de
lab head
Manuela Moritz
contact affiliation	Institute of Clinical Chemistry and Laboratory Medicine Section / Core Facility Mass Spectrometry and Proteomics
contact email	ma.moritz@uke.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053649
     1. Label: PRIDE project
     2. Name: Spatial proteomics reveals distinct protein patterns in a lissencephaly-like cortical migration disorder caused by LIN28A overexpression and WNT activation