Hypoxia-driven phase separation of the PABP1/eIF4B complex forms stress granules and activates ChaC2 translation to promote polyunsaturated lipids-supported peritoneal metastasis in gastric cancer - P
4 hours ago
- #Hypoxia
- #Ferroptosis
- #Gastric cancer
- Hypoxia-driven phase separation of PABP1/eIF4B complex forms stress granules and activates ChaC2 translation.
- ChaC2 is identified as a critical driver of peritoneal metastasis (PM) in gastric cancer (GC).
- ChaC2 attenuates ferroptosis sensitivity caused by elevated polyunsaturated fatty acids (PUFAs) levels in metastatic GC cells.
- Under hypoxic conditions, HIF-1α upregulates eIF4B and promotes PABP1 cytoplasmic translocation, leading to liquid-liquid phase separation (LLPS).
- The PABP1/eIF4B LLPS recruits G3BP1 to nucleate stress granules (SGs), enhancing ChaC2 mRNA stability and translational efficiency.
- This mechanism enables metastatic GC cells to evade ferroptosis and facilitates tumor dissemination.
- The study offers novel therapeutic targets and strategic insights for intervention in GC peritoneal metastasis.