Contribution of exosomal protein complexes to cell-cell communication
Exosomes, small membrane vesicles of endocytic origin, are secreted by most cell types. Although functioning as powerful intercellular communicators, the identity of exosomal protein complexes (EPCs) and their specific components, together with the molecular mechanisms underlying their functions in recipient cells, remain unknown. This project focuses on the hypothesis that multiprotein complexes contained in cancer cell-derived exosomes play a crucial role in cell-cell communication and that perturbation of EPCs may affect the functionality of stromal target cells.
This project will identify exosome protein complexes, their specific protein components and insights into their structural organization (i.e., core subunit interactions) and functionality in the context of cancer biology. Such complexes contained in cancer cell-derived exosomes play a crucial role in cell-cell communication and that perturbation of EPCs may affect target cell functionality and impact on exosome-targeted drug design.
This project will investigate the following questions:
(1) What are the different methods to isolate and biochemically characterize EPCs from human cancer cell models?
(2) Which proteins are contained within EPCs that contribute to their function? Can selected EPCs be perturbed by shRNA and/or overexpression of EPC protein subunits?
(3) What are the distinct functions of EPCs during cancer initiation, development, and metastasis?