PHGDH phosphorylation mediated by WNK1 serves as a dual marker of metabolic vulnerability and responsiveness to oxaliplatin treatment - PubMed
3 hours ago
- #PHGDH
- #WNK1
- #oxaliplatin-resistance
- Metabolic reprogramming is a key feature of cancer progression, with serine metabolism playing a significant role in gastric cancer (GC).
- Phosphoglycerate dehydrogenase (PHGDH) is upregulated in GC, and its activity is enhanced by phosphorylation at Ser349 and Ser371 by WNK1, increasing its stability.
- WNK1 knockout mice show reduced tumor burden, lower serine levels, and disrupted redox balance, indicating the WNK1-PHGDH axis's protumorigenic role.
- High PHGDH activity, elevated serine levels, and increased glutathione are linked to poor response to oxaliplatin in GC patients, suggesting PHGDH as a biomarker for chemotherapy resistance.
- The WNK1-PHGDH axis promotes redox adaptation and chemoresistance in GC, highlighting its dual role as a driver of cancer and a therapeutic target.