Neuronal and Glial YAP/TAZ in the Spinal Cord Contribute to the Development of Bone Cancer Pain in Mice

  • Neurosci Bull. 2026 Mar 22. doi: 10.1007/s12264-026-01607-4.
Bo Peng  #  1  2 ,  Xiaqing Lin  #  1  2 ,  Jiang-Jian Hu  1  2 ,  Huabao Liao  1  2 ,  Cheng Li  1  2 ,  Zhaoyu Li  3 ,  Xue-Jun Song  4  5
Affiliations
  • 1. Department of Medical Neuroscience, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.
  • 2. SUSTech Center for Pain Medicine, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.
  • 3. Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Australia.
  • 4. Department of Medical Neuroscience, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China. [email protected].
  • 5. SUSTech Center for Pain Medicine, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China. [email protected].
  • # Contributed equally.
PMID: 41866450 DOI: 10.1007/s12264-026-01607-4
Abstract

The treatment of bone Cancer pain (BCP) remains a major clinical challenge, and the mechanisms underlying BCP remain poorly understood. Here, we report that tumor cell implantation (TCI) led to nuclear accumulation of yes-associated protein (YAP) and transcriptional coactivator with PDZ (postsynaptic density protein 95, PSD-95; discs large, Dlg; zonula occludens-1, ZO-1)-binding motif (TAZ) and up-regulation of their mRNA (messenger ribonucleic acid) expression in Vglut2+ excitatory neurons, microglia, and astrocytes in the spinal dorsal horn. Pharmacological inhibition of YAP/TAZ or genetic knockout of YAP/TAZ in Vglut2+ excitatory neurons, microglia, or astrocytes significantly alleviates TCI-induced BCP. Mechanistically, ablation of YAP/TAZ in Vglut2+ excitatory neurons suppressed TCI-induced hyperexcitability of the dorsal horn neurons via β-catenin signaling modulation; concurrently, deletion of YAP/TAZ in microglia and astrocytes prevented TCI-induced activation of these glial cells and decreased levels of proinflammatory cytokines through regulation of nuclear factor kappa-B (NF-κB) signaling. The present study reveals the vital roles of spinal YAP/TAZ in the pathogenesis of BCP and identifies a potential molecular target for therapeutic intervention in BCP.

Keywords
Astrocytes; IL-1β; IL-6; Microglia; NF-κB; TNF-α; Vglut2+ excitatory neurons; β-catenin.
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