Loss of fatty acid-binding protein 7 enhances metastasis in B16F10 melanoma cells through phenotypic shift

Melanoma possesses the characteristic phenotypic plasticity, enhancing its metastatic formation and drug resistance. Lipid and fatty acid metabolism are usually altered to support melanoma progression and can be targeted for therapeutic development. Fatty acid binding protein 7 (FABP7) is highly expressed in melanomas and is shown to support its proliferation, migration, and invasion, but the mechanisms remain unclear. Our study aimed to link FABP7 to lipid metabolism and phenotypic shift in melanomas. We established the Fabp7 -knockout (KO) B16F10 melanoma cells, which showed an enhanced invasion through matrix-coated membrane, without significant change in proliferation. Similar outcomes were obtained when using RNA interference targeting FABP7. Fabp7 -KO cells injected into mice exhibited slower primary tumor growth, but formed higher metastatic foci count in the lungs. We also discovered a higher saturation in overall lipids, phosphatidylcholines, and triacylglycerols. We observed transcriptional shifts toward the invasive MITF ^Low /AXL ^High phenotype, with upregulation of transforming growth factor-beta (TGF-β) receptor mRNAs. In conclusion, FABP7 may help balancing lipid saturation and maintain the proliferative state of melanomas, mitigating invasiveness and metastatic formation.