The RASSF1C-HIF-1α axis drives macrophage lipid metabolism to promote pancreatic cancer - PubMed
6 hours ago
- #Hypoxia Signaling
- #Macrophage Metabolism
- #Pancreatic Cancer
- The study reveals the RASSF1C-HIF-1α axis drives macrophage lipid metabolism to promote pancreatic cancer (PAAD) progression.
- Under hypoxia, RASSF1C upregulation enhances glycolysis and lactate production, acidifying the tumor microenvironment and activating tumor-associated macrophages (TAMs).
- Lactate suppresses UFL1 in macrophages, impairing UFL1-mediated IRF7 UFMylation, which leads to IRF7 degradation via K48-linked ubiquitination and disrupts lipid metabolism.
- Clinical data from PDAC specimens show RASSF1C and HIF-1α are highly expressed and correlate negatively with UFL1 and IRF7, linking high RASSF1C to poor differentiation and advanced stage.
- The findings suggest targeting the RASSF1C-HIF-1α-lactate-UFL1-IRF7 axis could offer therapeutic strategies for combined metabolic and immune interventions in PAAD.