Endogenous inhibitors of PP2A activates oncogenic and DNA damage response kinases in glioblastoma - PubMed
3 hours ago
- #Radiation Therapy
- #Glioblastoma
- #PP2A
- Glioblastomas (GBMs) show constitutive activation of oncogenic kinase signaling pathways, leading to tumor aggressiveness and therapy resistance.
- Kinase inhibitors have limited efficacy in GBMs due to the tumors' adaptability and rewiring of signaling networks.
- GBMs inhibit tumor suppressor protein phosphatase 2A (PP2A) via overexpression of endogenous inhibitors (EIPs) like ANP32A, CIP2A, and SET.
- Inhibition of EIPs restores PP2A activity, disrupting oncogenic kinase activation and reducing tumor formation.
- CRISPR-Cas9 silencing of EIPs enhances PP2A's targeting of DNA damage response kinases ATR and ATM, sensitizing tumors to radiation.
- Activating PP2A in GBMs shows therapeutic potential, both alone and in combination with radiation.