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MerlinS13 phosphorylation regulates meningioma Wnt signaling and magnetic resonance imaging features

Author

Listed:
  • Charlotte D. Eaton

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Lauro Avalos

    (University of California San Francisco
    University of California San Francisco)

  • S. John Liu

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Zhenhong Chen

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Naomi Zakimi

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Tim Casey-Clyde

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Paola Bisignano

    (Vanderbilt University)

  • Calixto-Hope G. Lucas

    (Johns Hopkins University)

  • Erica Stevenson

    (California Institute for Quantitative Biosciences
    University of California San Francisco)

  • Abrar Choudhury

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Harish N. Vasudevan

    (University of California San Francisco
    University of California San Francisco)

  • Stephen T. Magill

    (Northwestern University)

  • Jacob S. Young

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Nevan J. Krogan

    (California Institute for Quantitative Biosciences
    University of California San Francisco)

  • Javier E. Villanueva-Meyer

    (University of California San Francisco
    University of California San Francisco)

  • Danielle L. Swaney

    (California Institute for Quantitative Biosciences
    University of California San Francisco)

  • David R. Raleigh

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

Abstract

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.

Suggested Citation

  • Charlotte D. Eaton & Lauro Avalos & S. John Liu & Zhenhong Chen & Naomi Zakimi & Tim Casey-Clyde & Paola Bisignano & Calixto-Hope G. Lucas & Erica Stevenson & Abrar Choudhury & Harish N. Vasudevan & S, 2024. "MerlinS13 phosphorylation regulates meningioma Wnt signaling and magnetic resonance imaging features," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52284-8
    DOI: 10.1038/s41467-024-52284-8
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    References listed on IDEAS

    as
    1. Farshad Nassiri & Jeff Liu & Vikas Patil & Yasin Mamatjan & Justin Z. Wang & Rupert Hugh-White & Andrew M. Macklin & Shahbaz Khan & Olivia Singh & Shirin Karimi & Rosario I. Corona & Lydia Y. Liu & Ca, 2021. "A clinically applicable integrative molecular classification of meningiomas," Nature, Nature, vol. 597(7874), pages 119-125, September.
    2. Krishna Chinthalapudi & Vinay Mandati & Jie Zheng & Andrew J. Sharff & Gerard Bricogne & Patrick R. Griffin & Joseph Kissil & Tina Izard, 2018. "Lipid binding promotes the open conformation and tumor-suppressive activity of neurofibromin 2," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
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