| Autor: |
Eaton, Charlotte D., Avalos, Lauro, Liu, S. John, Chen, Zhenhong, Zakimi, Naomi, Casey-Clyde, Tim, Bisignano, Paola, Lucas, Calixto-Hope G., Stevenson, Erica, Choudhury, Abrar, Vasudevan, Harish N., Magill, Stephen T., Young, Jacob S., Krogan, Nevan J., Villanueva-Meyer, Javier E., Swaney, Danielle L., Raleigh, David R. |
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| Zdroj: |
Nature Communications; 9/9/2024, Vol. 15 Issue 1, p1-14, 14p |
| Abstrakt: |
Meningiomas are associated with inactivation of NF2/Merlin, but approximately one-third of meningiomas with favorable clinical outcomes retain Merlin expression. Biochemical mechanisms underlying Merlin-intact meningioma growth are incompletely understood, and non-invasive biomarkers that may be used to guide treatment de-escalation or imaging surveillance are lacking. Here, we use single-cell RNA sequencing, proximity-labeling proteomic mass spectrometry, mechanistic and functional approaches, and magnetic resonance imaging (MRI) across meningioma xenografts and patients to define biochemical mechanisms and an imaging biomarker that underlie Merlin-intact meningiomas. We find Merlin serine 13 (S13) dephosphorylation drives meningioma Wnt signaling and tumor growth by attenuating inhibitory interactions with β-catenin and activating the Wnt pathway. MRI analyses show Merlin-intact meningiomas with S13 phosphorylation and favorable clinical outcomes are associated with high apparent diffusion coefficient (ADC). These results define mechanisms underlying a potential imaging biomarker that could be used to guide treatment de-escalation or imaging surveillance for patients with Merlin-intact meningiomas. The molecular mechanisms underlying merlin-intact meningioma growth remain to be explored. Here, the authors show that merlin activates Wnt signalling and tumour growth through its dephosphorylation on serine 13 attenuating the inhibitory interactions with β-catenin. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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