Kinome and phosphoproteome of high-grade meningiomas reveal AKAP12 as a central regulator of aggressiveness and its possible role in progression

Carolina Angelica Parada, Joshua Osbun, Sumanpreet Kaur, Youssef Yakkioui, Min Shi, Catherine Pan, Tina Busald, Yigit Karasozen, Luis Francisco Gonzalez-Cuyar, Robert Rostomily, Jing Zhang, Manuel Ferreira

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Abstract

There is a need to better understand meningioma oncogenesis for biomarker discovery and development of targeted therapies. Histological or genetic criteria do not accurately predict aggressiveness. Post-translational studies in meningioma progression are lacking. In the present work, we introduce a combination of mass spectrometry-based phosphoproteomics and peptide array kinomics to profile atypical and anaplastic (high-grade) meningiomas. In the discovery set of fresh-frozen tissue specimens (14), the A-kinase anchor protein 12 (AKAP12) protein was found downregulated across the grades. AKAP12 knockdown in benign meningioma cells SF4433 increases proliferation, cell cycle, migration, invasion, and confers an anaplastic profile. Differentially regulated pathways were characteristic of high-grade meningiomas. Low AKAP12 expression in a larger cohort of patients (75) characterized tumor invasiveness, recurrence, and progression, indicating its potential as a prognostic biomarker. These results demonstrate AKAP12 as a central regulator of meningioma aggressiveness with a possible role in progression.

Original languageEnglish
Article number2098
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

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    Parada, C. A., Osbun, J., Kaur, S., Yakkioui, Y., Shi, M., Pan, C., Busald, T., Karasozen, Y., Gonzalez-Cuyar, L. F., Rostomily, R., Zhang, J., & Ferreira, M. (2018). Kinome and phosphoproteome of high-grade meningiomas reveal AKAP12 as a central regulator of aggressiveness and its possible role in progression. Scientific reports, 8(1), [2098]. https://doi.org/10.1038/s41598-018-19308-y