Rab23 activities and human cancer-emerging connections and mechanisms

Unlike founding members of the Ras superfamily of small GTPases that are prominently known for oncogenic signaling, members of the Rab subfamily are key regulators of cellular membrane traffic. However, a number of Rabs have in recent years also been strongly implicated as tumorigenic or metastatic biomarkers. Rab23 is an emerging example whose differential expression in tumor cells and functional association with proliferation and invasiveness is attracting attention as a useful cancer marker and a potential therapeutic target. Rab23 is ubiquitously expressed but appears to be particularly enriched in the adult brain. It has important developmental functions in vertebrates and has been shown to modulate Sonic hedgehog (Shh) and Nodal signaling. Although its exact cellular role in membrane traffic regulation remains elusive, its known role in Shh signaling, in conjunction with several recent findings, has clearly implicated a role for Rab23 in transport processes to the primary cilium. In this review, we summarize what is currently known about Rab23 as a cancer marker and discuss possible mechanism by which this Rab GTPase may act as an oncogenic or metastatic driver, while exhibiting tumor suppressive activity in some cases.