Ginkgetin targets GRP78 to induce dual pathways of ER stress and immune activation in osteosarcoma - PubMed
3 hours ago
- #immune activation
- #GRP78
- #osteosarcoma
- Ginkgetin (Gink) targets GRP78, a critical regulator of osteosarcoma progression.
- Gink directly binds to GRP78, with K296 as a key interaction site, disrupting GRP78-PERK interaction.
- Gink activates the PERK-eIF2α-ATF4 pathway, inducing apoptosis and autophagy in osteosarcoma cells.
- In vitro, Gink suppresses osteosarcoma cell proliferation, migration, and invasion.
- In vivo, Gink attenuates tumor growth and metastasis in orthotopic and patient-derived xenograft models.
- Gink reprograms the tumor immune microenvironment by reducing M2 macrophage polarization.
- Gink synergizes with anti-PD1 therapy to enhance CD8+ T-cell activity.
- Gink offers a dual-pronged therapeutic strategy against osteosarcoma by triggering ER stress and immune activation.