Longevity & AgingINHBA Protein Fuels Colorectal Cancer by Hijacking Immunity and Blocking Cell Death
Researchers at Central South University identified Inhibin beta A (INHBA) as a key driver of colorectal cancer (CRC) progression. Elevated INHBA expression correlates with worse survival in CRC patients. Mechanistically, INHBA stabilizes the mitochondrial transporter SLC25A10 by blocking its ubiquitin-mediated degradation via TRIM21. This stabilization enables tumor cells to export succinate, which binds the SUCNR1 receptor on macrophages, converting them to immune-suppressive M2 tumor-associated macrophages. Simultaneously, SLC25A10 shuttles glutathione into mitochondria, activating the mtGSH/GPX4 axis and suppressing ferroptosis. Together these dual mechanisms accelerate CRC growth and metastasis, positioning INHBA and its downstream effectors as promising therapeutic targets.
