Rab25 suppresses colon cancer cell invasion through upregulating claudin-7 expression

Abstract

Abstract Purpose Ras-related protein 25 (Rab25) is a member of small GTPase and implicated in various cancer cell progression. Growing evidence suggests the context-dependent roles of Rab25 in cancer invasiveness. Claudin-7 is a tight junction protein and has been known to suppress cancer cell invasion. Although Rab25 was reported to repress cancer aggressiveness through recycling β1 integrin to the plasma membrane, the detailed underlying mechanism remain unanswered. In the present study, we identify the critical role of claudin-7 in Rab25-induced suppression of colon cancer invasion. Methods To define the role of Rab25 and claudin-7 in colon cancer cells, we performed plasmid transfection and analyzed cancer cell invasion by utilizing 2D and 3D Matrigel invasion chambers. Immunoblotting, immunofluorescence and ELISA assay were used to identify the level of protein expression and pathways implicated in Rab25-induced colon cancer cell invasion. Results Enforced expression of Rab25 attenuates colon cancer cell invasion. In addition, Rab25 inactivated epidermal growth factor receptor (EGFR) and increased E-cadherin expression. Unexpectedly, we observed that Rab25 induces claudin-7 expression through protein stabilization. Moreover, ectopic expression of claudin-7 reduced EGFR activity and Snail expression as well as colon cancer cell invasion. However, silencing of claudin-7 expression reversed the tumor suppressive role of Rab25, thereby increasing colon cancer cell invasiveness. Conclusion Collectively, the present data indicate that Rab25 inactivates EGFR and colon cancer cell invasion through upregulating claudin-7 expression.