Mitochondrial-Localized Keratin 17 Promotes Chemoresistance in Basal-Like Pancreatic Cancer - PubMed
7 hours ago
- #Pancreatic Cancer
- #Mitochondrial Biology
- #Chemoresistance
- Mitochondrial-localized keratin 17 (K17) drives chemoresistance in basal-like pancreatic ductal adenocarcinoma (PDAC).
- K17 translocates into the mitochondrial intermembrane space via TOM20 recognition of its mitochondrial localization sequence (MLS).
- Inside mitochondria, K17 stabilizes dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine biosynthesis, by preventing its ubiquitination-mediated degradation.
- Blocking K17 mitochondrial entry sensitizes cancer cells to gemcitabine, a standard chemotherapy drug.
- Pharmacological DHODH inhibition combined with gemcitabine reduces tumor growth and improves survival in K17-positive PDAC mouse models.
- The findings reveal a metabolic vulnerability in K17-positive basal-like PDACs, offering a potential therapeutic target.