Rab GTPases as potential tumor suppressors

Abstract

The Ras-associated binding (Rab) family of small GTPases serves as molecular switches in regulating vesicular membrane traffic in all eukaryotic cells. Although not conventionally categorized as oncogenes or tumor suppressors, aberrant expressions of several members of the Rab family in cancer tissues have nonetheless been noted. Recent findings have highlighted the potential of certain Rab family members acting both as oncogenic drivers, as well as tumor suppressors. Rab25's expression status, for example, could be an important determinant of progression and aggressiveness of breast and ovarian cancers. Paradoxically, its over-expression could also be tumor-suppressive. In general, deregulation of Rab expression could perturb proliferative or survival signaling pathways through spatial and temporal changes in growth factor receptor traffic and associated signaling. Furthermore, aberrant expression of Rabs may affect the modulation of the dynamics of cell adhesion components (such as integrins) and the cytoskeleton. This may in turn affect cancer cell migration, invasion and metastasis. Finally, deregulation of Rabs that are important in the differentiation of progenitor cells may impair differentiation and enhance tumorigenesis. We discuss in this chapter recent findings implicating Rabs in a variety of human cancers, and explore in particular, plausible mechanisms of how Rabs could be tumor-suppressive. © 2011 by Nova Science Publishers, Inc. All rights reserved.