CAV1-DOT1L axis in TAM-derived EVs orchestrates VM and sensitises PDAC to combined VM and VEGF targeting - PubMed
2 hours ago
- #Pancreatic Cancer
- #Tumor Microenvironment
- #Vasculogenic Mimicry
- Vasculogenic mimicry (VM) is crucial for pancreatic ductal adenocarcinoma (PDAC) perfusion and metastasis.
- Tumor-associated macrophages (TAMs) promote VM, tube formation, invasion, and tumor growth via extracellular vesicles (EVs).
- EV proteomics identified caveolin-1 (CAV1) as a key cargo correlating with VM density and TAM infiltration.
- CAV1 interacts with DOT1L, promoting H3K79 methylation-dependent ATG5 transcription, sustaining VM and invasive phenotypes.
- DOT1L inhibition suppresses VM but induces compensatory endothelial angiogenesis.
- Combined DOT1L and VEGFR blockade effectively controls tumor progression without toxicity.
- Dual targeting of VM and angiogenesis presents a promising therapeutic strategy for PDAC.