Circulating FABP4 promotes obesity-associated breast cancer lung metastasis through PIP2.

Obesity increases breast cancer lung metastasis in high-fat diet-induced obesity models via elevated adipocyte-derived circulating FABP4, with FABP4/PIP2 driving migration through PKC and mitochondrial ROS.

• Why it matters: The molecular link between obesity and breast cancer progression is not fully defined, limiting targeted strategies to reduce obesity-associated metastatic risk.
• What they did: Using several high-fat diet-induced obesity models, the study shows circulating FABP4 directly binds a subset of breast cancer cells through membrane lipid PIP2, activating PKC signaling and boosting mitochondrial ROS to promote migration.
• The result: Global or adipocyte-specific FABP4 deletion markedly reduces obesity-associated metastasis, and neutralizing circulating FABP4 with a monoclonal antibody significantly suppresses metastasis across multiple preclinical models.

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