Abstract

Inhibition of Exosome Secretion in Cancer Cells by an Antibiotic

Moon-Chang Baek, Director, Exosome Convergence Research Center (ECRC), Kyungpook National University School of Medicine

Inhibitors of the secretion of cancer exosomes, which promote cancer progression and metastasis, may not only accelerate exosome biology research but also offer therapeutic benefits for cancer patients. We identify sulfisoxazole (SFX) as an inhibitor of small extracellular vesicles (sEV) secretion from breast cancer cells through interference with endothelin receptor A (ETA). SFX, an FDA-approved oral antibiotic, showed significant anti-tumor and anti-metastatic effects in mouse models of breast cancer xenografts, reduced the expression of proteins involved in biogenesis and secretion of sEV, and triggered co-localization of multivesicular endosomes with lysosomes for degradation. The important role of ETA, as a newly-identified target of SFX, is demonstrated by gain- and loss-of-function studies of ETA protein through a direct binding assay, pharmacological and genetic approaches. These findings may provide a foundation for sEV-targeted cancer therapies and the mechanistic studies on sEV biology.