The role of the small <scp>GTP</scp> ase Rab31 in cancer

<jats:title>Abstract</jats:title> <jats:p> Members of the small <jats:styled-content style="fixed-case">GTP</jats:styled-content> ase family Rab are emerging as potentially important factors in cancer development and progression. A good number of Rabs have been implicated or associated with various human cancers, and much recent excitement has been associated with the roles of the Rab11 subfamily member Rab25 and its effector, the Rab coupling protein ( <jats:styled-content style="fixed-case">RCP</jats:styled-content> ), in tumourigenesis and metastasis. In this review, we focus on a Rab5 subfamily member, Rab31, and its implicated role in cancer. Well recognized as a breast cancer marker with good prognostic value, recent findings have provided some insights as to the mechanism underlying Rab31's influence on oncogenesis. Levels of Oestrogen Receptor α ( <jats:styled-content style="fixed-case">ER</jats:styled-content> α)‐ responsive Rab31 could be elevated through stabilization of its transcript by the <jats:styled-content style="fixed-case">RNA</jats:styled-content> binding protein HuR, or though activation by the oncoprotein mucin1‐C ( <jats:styled-content style="fixed-case">MUC</jats:styled-content> 1‐C), which forms a transcriptional complex with <jats:styled-content style="fixed-case">ER</jats:styled-content> α. Elevated Rab31 stabilizes <jats:styled-content style="fixed-case">MUC</jats:styled-content> 1‐C levels in an auto‐inductive loop that could lead to aberrant signalling and gene expression associated with cancer progression. Rab31 and its guanine nucleotide exchange factor <jats:styled-content style="fixed-case">GAP</jats:styled-content> ex‐5 have, however, also been shown to enhance early endosome‐late endosome transport and degradation of the epidermal growth factor receptor (EGFR). The multifaceted action and influences of Rab31 in cancer is discussed in the light of its new interacting partners and pathways. </jats:p>