Investigating YAP-dependent angiogenesis in glioblastoma

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Glioblastoma multiforme (GBM) is an aggressive brain tumor characterized by significant angiogenesis.
• YAP/TAZ proteins are crucial for vascular development and are implicated in various cancers.
• Dysregulation of YAP/TAZ is linked to cancer progression and poor prognosis.

Purpose of the Study:

• To investigate the interplay between the Hippo and VEGF signaling pathways in GBM.
• To evaluate the role of the Hippo pathway transducer Yap1 in GBM angiogenesis.
• To explore the potential of targeting the Hippo-YAP1 signaling axis for anti-angiogenic therapy in GBM.

Main Methods:

• Weighted gene co-expression network analysis (WGCNA) to identify relevant gene modules in GBM.
• CRISPR/Cas9-mediated Yap1 knockout in C6 GBM cells and development of a rat GBM model.
• Assays including CAM assay, immunohistochemistry (IHC), and qPCR to assess angiogenic effects and gene expression.

Main Results:

• Identified RELA and NF-κB as shared transcription factors between Hippo and VEGF pathways in GBM.
• Yap1 knockout in GBM cells significantly reduced vessel length in CAM assays.
• Yap1 knockout in rat GBM models demonstrated reduced vessel density, neoformation, and VEGF expression.

Conclusions:

• The Hippo pathway transducer Yap1 plays a significant role in GBM angiogenesis.
• Targeting the Hippo-YAP1 signaling pathway holds potential for enhancing anti-angiogenic strategies in GBM treatment.