A central role for vesicle trafficking in epithelial neoplasia: intracellular highways to carcinogenesis.

Abstract

Epithelial cell carcinogenesis involves the loss of cell polarity, alteration of polarized protein presentation, dynamic cell morphology changes, increased proliferation, and increased cell motility and invasion. Membrane vesicle trafficking underlies all of these processes. Specific membrane trafficking regulators, including RAB small GTPases, through the coordinated dynamics of intracellular trafficking along cytoskeletal pathways, determine the cell surface presentation of proteins and the overall function of both differentiated and neoplastic cells. Although mutations in vesicle trafficking proteins may not be direct drivers of transformation, components of the machinery of vesicle movement have crucial roles in the phenotypes of neoplastic cells. Therefore, the regulators of membrane vesicle trafficking decisions are essential mediators of the full range of cell physiologies that drive cancer cell biology, including initial loss of cell polarity, invasion and metastasis. Targeting of these fundamental intracellular processes may permit the manipulation of cancer cell behaviour.