PXD053578

PXD053578 is an original dataset announced via ProteomeXchange.

Title	Merlin S13 phosphorylation controls meningioma Wnt signaling and magnetic resonance imaging features
Description	Meningiomas are the most common primary intracranial tumors and are associated with inactivation of the tumor suppressor NF2/Merlin, but one-third of meningiomas retain Merlin expression and typically have favorable clinical outcomes. Biochemical mechanisms underlying Merlin-intact meningioma growth are incompletely understood, and non-invasive biomarkers that predict meningioma outcomes and could be used to guide treatment de-escalation or imaging surveillance of Merlin-intact meningiomas are lacking. Here we integrate single-cell RNA sequencing, proximity-labeling proteomic mass spectrometry, mechanistic and functional approaches, and magnetic resonance imaging (MRI) across meningioma cells, xenografts, and human patients to define biochemical mechanisms and an imaging biomarker that distinguish Merlin-intact meningiomas with favorable clinical outcomes from meningiomas with unfavorable clinical outcomes. We find Merlin drives meningioma Wnt signaling and tumor growth through a feed-forward mechanism that requires Merlin dephosphorylation on serine 13 (S13) to attenuate inhibitory interactions with β-catenin and activate the Wnt pathway. Meningioma MRI analyses of xenografts and human patients show Merlin-intact meningiomas with S13 phosphorylation and favorable clinical outcomes are associated with high apparent diffusion coefficient (ADC) on diffusionweighted imaging. In sum, our results shed light on Merlin posttranslational modifications that regulate meningioma Wnt signaling and tumor growth in tumors without NF2/Merlin inactivation. To translate these findings to clinical practice, we establish a non-invasive imaging biomarker that could be used to guide treatment de-escalation or imaging surveillance for patients with favorable meningiomas.
HostingRepository	PRIDE
AnnounceDate	2024-07-04
AnnouncementXML	Submission_2024-07-03_22:36:38.305.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Justin McKetney
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-02 14:15:37	ID requested
⏵ 1	2024-07-03 22:36:39	announced

10.21203/rs.3.rs-2577844/v1;

Eaton C, Avalos L, Liu SJ, Casey-Clyde T, Bisignano P, Lucas CH, Stevenson E, Choudhury A, Vasudevan H, Magill S, Krogan N, Villanueva-Meyer J, Swaney D, Raleigh D, phosphorylation controls meningioma Wnt signaling and magnetic resonance imaging features. Res Sq, ():(2023) [pubmed]

submitter keyword: Wnt signaling, proximity labeling, meningioma, MRI, phosphoproteomics

Nevan Krogan
contact affiliation	University of California, San Francisco
contact email	nevan.krogan@ucsf.edu
lab head
Justin McKetney
contact affiliation	University of California, San Francisco
contact email	justinmcketney@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053578
     1. Label: PRIDE project
     2. Name: Merlin S13 phosphorylation controls meningioma Wnt signaling and magnetic resonance imaging features