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Published on: October 11, 2022
Rab25 suppresses colon cancer cell invasion through upregulating claudin‑7 expression
Su Jin Cho1, Bo Young Jeong2, Se-Hee Yoon3
1Department of Pharmacology, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea.
Abstract:
Ras‑related protein 25 (Rab25) is a member of small GTPase and is implicated in cancer cell progression of various types of cancer. Growing evidence suggests the context‑dependent role 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 remains to be elucidated. The present study identified the critical role of claudin‑7 in Rab25‑induced suppression of colon cancer invasion. 3D Matrigel system and modified Boyden chamber analysis showed that enforced expression of Rab25 attenuated colon cancer cell invasion. In addition, Rab25 inactivated epidermal growth factor receptor (EGFR) and increased E‑cadherin expression. Unexpectedly, it was observed that Rab25 induces claudin‑7 expression through protein stabilization. In addition, ectopic claudin‑7 expression 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. Collectively, the present data indicated that Rab25 inactivates EGFR and colon cancer cell invasion by upregulating claudin‑7 expression.
Insights
Ras-related protein 25 (Rab25) suppresses colon cancer invasion by stabilizing claudin-7. This upregulation reduces EGFR activity and E-cadherin expression, inhibiting tumor cell movement and progression.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Ras-related protein 25 (Rab25), a small GTPase, plays a context-dependent role in cancer progression and invasiveness.
- Claudin-7, a tight junction protein, is known to suppress cancer cell invasion.
- The precise mechanism by which Rab25 inhibits cancer aggressiveness requires further elucidation.
Purpose of the Study:
- To investigate the role of claudin-7 in Rab25-mediated suppression of colon cancer invasion.
- To elucidate the molecular mechanisms underlying Rab25's effect on colon cancer cell invasiveness.
Main Methods:
- Utilized 3D Matrigel invasion assays and modified Boyden chamber analysis.
- Investigated the effects of Rab25 expression on epidermal growth factor receptor (EGFR) and E-cadherin.
- Examined the impact of Rab25 on claudin-7 expression and stability.
- Assessed the role of claudin-7 in modulating EGFR activity, Snail expression, and colon cancer cell invasion.
Main Results:
- Enforced Rab25 expression attenuated colon cancer cell invasion.
- Rab25 inactivated EGFR and increased E-cadherin expression.
- Rab25 induced claudin-7 expression via protein stabilization.
- Ectopic claudin-7 expression reduced EGFR activity, Snail expression, and colon cancer cell invasion.
- Silencing claudin-7 reversed the tumor-suppressive effects of Rab25, increasing invasiveness.
Conclusions:
- Rab25 suppresses colon cancer cell invasion by upregulating claudin-7 expression.
- The Rab25-claudin-7 axis inactivates EGFR, thereby inhibiting colon cancer cell invasion.
- Claudin-7 is a critical mediator of Rab25's tumor-suppressive function in colon cancer.
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