PXD053578 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-07-02 14:15:37 | ID requested | |
⏵ 1 | 2024-07-03 22:36:39 | announced | |
Publication List
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] |
Keyword List
submitter keyword: Wnt signaling, proximity labeling, meningioma, MRI, phosphoproteomics |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD053578
- Label: PRIDE project
- Name: Merlin S13 phosphorylation controls meningioma Wnt signaling and magnetic resonance imaging features