1054-Palmitic Acid in Breast Cancer Lung Metastasis

The research examines how palmitic acid (PA) facilitates the spread of triple-negative breast cancer to the lungs by modifying the local environment before tumor cells even arrive. The study identifies that pulmonary endothelial cells serve as a primary source of PA, which triggers neutrophils to release the protein lipocalin-2 (LCN2) via the TLR4-NF-κB signaling pathway. This process degrades vascular tight junctions, specifically targeting ZO-1, thereby compromising the blood vessel barrier and allowing circulating cancer cells to exit into the lung tissue. Furthermore, the researchers discovered that LCN2 promotes the formation of neutrophil extracellular traps (NETs) and creates an immunosuppressive niche that protects metastatic colonies. To address this, the authors demonstrate that GLP-1 receptor agonists can reduce metastasis by inhibiting fatty acid synthesis in the lung’s blood vessels. This comprehensive analysis highlights the potential for metabolic interventions to prevent organ-specific cancer dissemination by preserving vascular integrity.

References:

• Qian P, Li Y, Han Y, et al. Palmitic acid reprograms neutrophils to compromise vascular integrity and promote breast cancer lung metastasis[J]. Immunity, 2026.