Metabolic regulation of exosome biogenesis as a determinant of cancer cell metastasis.

The studies will examine the mechanisms by which aggressive breast cancer cells generate exosomes with unique cargo and a total secretome that enhances metastatic potential. Key areas of investigation include: 1) the relationship between SIRT1 down-regulation, elevated glutamine metabolism, and the generation of exosomes with unique cargo; 2) how SIRT1 down-regulation impacts vacuolar ATPase expression to produce a secretome promoting cancer cell invasiveness; and 3) how SIRT1 expression/activity affects exosome production, cell invasiveness, and metastatic spread in breast cancer models. The research will utilize multi-disciplinary expertise in biochemical and chemical biology, high-resolution imaging, 3D spheroid culture, tumor organoids, and mouse models.