Abstract 5419: Claudin-7 mediates Rab25-induced suppression of colon cancer cell invasion

Abstract

Abstract Ras-related protein 25 (Rab25) is a member of small GTPase, and growing evidence demonstrates the context-dependent roles of Rab25 in cancer progression. While Rab25 aggravates cancer cell invasion in ER-positive breast, ovarian, and gastric cancers, Rab25 is under-expressed and suppresses colon and triple-negative breast cancer progression. Claudins are major components of tight junctions, and disruption of claudins is implicated in tumorigenesis. Among 27 known members of the claudin family, claudin-7 is suggested to suppress colon cancer progression. Previously, we identified that Rab25 induces endothelial-mesenchymal transition (EMT) and invasiveness of several types of cancer cells through activating the β1 integrin/epidermal growth factor receptor (EGFR)/Snail signaling cascades. However, little is known about the underlying mechanism of Rab25-induced tumor suppression. In the present study, we identify the critical role of claudin-7 in Rab25-induced suppression of colon cancer invasion. 3D Matrigel and modified Boden chamber were used to assess the invasiveness of colon cancer cells. Wound-healing assay was used to analyze colon cancer cell migration. 3D Matrigel was used to analyze tumor growth. Immunoblotting was used to assess the protein expression. Rab25 induced claudin-7 expression in colon cancer cells through protein stabilization. In addition, the enforced expression of claudin-7 not only reduced the EGFR/Ras signaling activity and Snail expression but also attenuated colon cancer cell invasion. However, silencing of claudin-7 expression rescued the tumor suppressive role of Rab25, thereby increasing colon cancer cell invasiveness. Collectively, our data demonstrate for the first time that Rab25 reduces the EGFR/Ras/Snail signaling activity and inhibits colon cancer cell invasion by upregulating claudin-7 expression. Citation Format: Su Jin Cho, Bo Young Jeong, Se-Hee Yoon, Chang Gyo Park, Hoi Young Lee. Claudin-7 mediates Rab25-induced suppression of colon cancer cell invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5419.