Rab25 GTPase: Functional roles in cancer

Abstract

Rab25, a small GTPase belongs to the Rab protein family, has a pivotal role in cancer pathophysiology. Rab25 governs cell-surface receptors recycling and cellular signaling pathways activation, allowing it to control a diverse range of cellular functions, including cell proliferation, cell motility and cell death. Aberrant expression of Rab25 was linked to cancer development. Majority of research findings revealed that Rab25 is an oncogene. Elevated expression of Rab25 was correlated with poor prognosis and aggressiveness of renal, lung, breast, ovarian and other cancers. However, tumor suppressor function of Rab25 was reported in several cancers, such as colorectal cancer, indicating the tumor type-specific function of Rab25. In this review, we recapitulate the current knowledge of Rab25 in cancer development and therapy.

Keywords: Rab25; ovarian cancer; renal cancer; small GTPase; vesicle trafficking.

Figure 1. Schematic diagram of Rab GTPase cycle

Rabs switch between two conformations, an inactive GDP-bound form and an active GTP-bound form. A guanine nucleotide exchange factor (GEF) catalyzes the conversion from GDP-bound to GTP-bound and leads to activation of Rab. Activated Rab binds with specific effectors to promote vesicle trafficking. The inherent GTP hydrolysis of Rabs together with the enhancing effect of GTPase-activating protein (GAP) leads to Rab inactivation. Conversion of Rabs to the inactive state leads to effector dissociation from the Rab protein.

Figure 2. Overview of Rab25 functions in the cells

Rab25 regulates apical recycling of α5β1 integrin containing endosome. Suppressive effect of Rab25 on BAX and BAK leads to reduction of apoptotic cell death. Direct Rab25 / α5β1 integrin interaction and Rab25 induced activation of Akt, Src and Wnt pathways are associated with cell growth, metastasis and chemoresistance of cancer cells.