FAM135B suppresses glioblastoma angiogenesis via stabilizing the IKK complex and inactivating the NF-κB/IL-6 signaling pathway - PubMed
4 hours ago
- #Glioblastoma angiogenesis
- #FAM135B mechanism
- #NF-κB signaling
- FAM135B is a brain-enriched protein that acts as a negative regulator of angiogenesis in glioblastoma (GBM).
- Low FAM135B expression correlates with poor prognosis, high angiogenic potential, and increased endothelial cell communication in GBM patients.
- FAM135B overexpression inhibits angiogenesis in vitro (HUVEC tube formation, migration) and in vivo (reduced tumor growth, microvessel formation, prolonged survival).
- FAM135B binds to and stabilizes the IKK complex (IKKα/IKKβ), inhibiting NF-κB signaling and downstream IL-6 expression.
- IL-6 reduction by FAM135B inhibits the JAK/STAT pathway in endothelial cells, suppressing angiogenesis.
- HNF4A is the upstream transcription factor that promotes FAM135B expression, and its overexpression also inhibits angiogenesis, dependent on FAM135B.
- Targeting the HNF4A/FAM135B/NF-κB/IL-6 axis offers a novel therapeutic strategy for anti-angiogenic therapy in GBM.