Highlight
– MTFP1 identified as a key driver of pancreatic ductal adenocarcinoma (PDAC) liver metastasis via regulation of mitochondrial oxidative phosphorylation.
– MTFP1 interacts with ATP synthase subunits, enhancing oxidative phosphorylation and increasing mitochondrial fission.
– Upregulated reactive oxygen species (ROS) trigger the PI3K/AKT/c-MYC/SLC1A5 pathway, promoting glutamine uptake that supports tumor growth and suppresses CD8+ T-cell antitumor responses.
– Inhibition of MTFP1 or limiting glutamine uptake reverses the immunosuppressive tumor microenvironment (TME) and reduces liver colonization in PDAC.
– Identification of KPT 9274 (ATG-019) as a potential MTFP1 inhibitor offers a novel therapeutic avenue for PDAC patients with liver metastases.
