Rab25 as a tumour suppressor in colon carcinogenesis

Abstract

Recent investigations have increasingly focussed attention on the roles of intracellular vesicle trafficking in the regulation of epithelial polarity and transformation. Rab25, an epithelial-specific member of the Rab family of small GTPases, has been associated with several epithelial cancers. Whereas Rab25 overexpression is associated with ovarian cancer aggressive behaviour, Rab25 expression is decreased in human colon cancers independent of stage. Recent studies of mouse models of intestinal and colonic neoplasia have demonstrated that Rab25 deficiency markedly promotes the development of neoplasia. Some of these effects appear related to alterations in β1-integrin trafficking to the cell surface. These findings all suggest that Rab25 is a tumour suppressor for colonic neoplasia.

Figure 1

A scheme for regulation of transformation and cell polarity by Rab25. The figure shows the possible interactions of vesicle recycling through recycling endosomes (RE) of either signalling receptors (on the left) or polarity-related proteins (on the right). Loss of Rab25 in colon cells could lead to either direct dysregulation of these pathways or imbalances in parallel trafficking pathways regulated by Rab11a or by alteration of influences on downstream shared effectors such as Rab11-FIP1C (also known as RCP). Effects of Rab25 on transcription remain unknown, although there is no evidence that Rab25 ever enters the nucleus.