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

Cho,Su Jin; Jeong,Bo Young; Yoon,Se-Hee; Park,Chang Gyo; Lee,Hoi Young

doi:10.3892/or.2023.8685

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

Authors:
- Su Jin Cho
- Bo Young Jeong
- Se-Hee Yoon
- Chang Gyo Park
- Hoi Young Lee
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Affiliations: Department of Pharmacology, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea, Department of Cell, Developmental and Cancer Biology, School of Medicine, Oregon Health Science University, Portland, OR 97201, USA, Division of Nephrology and Department of Internal Medicine, College of Medicine, Konyang University, Daejeon 35364, Republic of Korea
Published online on: December 18, 2023 https://doi.org/10.3892/or.2023.8685
Article Number: 26
Copyright: © Cho et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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