Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin

The small GTP-binding protein Rab25 is associated with tumor formation and progression. However, recent studies have shown discordant effects of Rab25 on cancer cell progression depending on cell lineage. In the present study, we elucidate the underlying mechanisms by which Rab25 induces cellular invasion. We demonstrate that Rab25 increases β1 integrin levels and subsequent activation of EGFR and upregulation of VEGF-A expression, leading to increased Snail expression, epithelial-to-mesenchymal transition and cancer cell invasiveness. Strikingly, we identify that Snail mediates Rab25-induced cancer cell invasiveness through fascin expression and that ectopic expression of Rab25 aggravates metastasis of ovarian cancer cells to the lung. We thus demonstrate a novel role of a β1 integrin/EGFR/VEGF-A/Snail signaling cascade in Rab25-induced cancer cell aggressiveness through induction of fascin expression, thus providing novel biomarkers and potential therapeutic targets for Rab25-expressing cancer cells. Researchers have unraveled the details of how the protein Rab25 promotes invasiveness of some cancers. Rab25 had been reported to promote the spread of some cancers and inhibit others, but the reason for its contradictory effects was unclear. Hoi Young Lee at Konyang University in Daejeon, South Korea and co-workers examined the mechanism by which Rab25 promotes cancer cell invasiveness, to investigate why it promotes only certain cancers. Using genetic analysis and mouse model testing, the researchers found that Rab25 switches on a signaling pathway that triggers cancer cells to detach from the tumor and spread to other organs. Increasing the levels of Rab25 also increased the invasiveness of breast, ovarian and gastric cancer cells. These results could help to identify new biomarkers and potential therapeutic targets for cancers that express Rab25.