YAP-TEAD-driven CPA4 promotes NF2-deficient meningioma growth

Authors

Mineji, K., Petrosky, K., Otsuji, R., Makino, Y., Kibe, Y., Uchida, E., Hagita, D., Singaravelan, N., Ishi, Y., Yamaguchi, S., Chang, L.-S., Gadd, S., Hashizume, R.

Abstract

Neurofibromin 2 (NF2) deficiency is a driver of meningioma and other cancers, yet transcriptional effectors that sustain NF2-deficient tumors remain poorly defined. We identify carboxypeptidase A4 (CPA4) as an effector of YAP-TEAD signaling in NF2-deficient meningioma. Transcriptomic profiling identified CPA4 as a consistently upregulated effector. Across patient cohorts and specimens, CPA4 expression was enriched in NF2-mutant and chromosome 22q-deleted meningiomas and associated with higher tumor grade and chromosome 1p loss. CPA4 depletion impaired proliferation, disrupted cell-cycle, DNA-replication, and DNA-repair programs, suppressed intracranial tumor growth, and prolonged survival. Integrated epigenomic and functional assays identified CPA4 as a direct YAP-TEAD transcriptional target. CPA4-high meningioma models exhibited preferential sensitivity to YAP-TEAD inhibition, while verteporfin and the clinical-stage TEAD inhibitor VT3989 reduced CPA4 expression, suppressed orthotopic tumor growth, and prolonged survival. These findings uncover a targetable YAP-TEAD-CPA4 dependency in NF2-deficient meningioma and identify CPA4 as a potential biomarker for TEAD-directed therapy.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 09 Aug 2026.

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