Abstract 2485: RAB31 interacts with AGR2 to respond to oxaliplatin resistance and epithelial-mesenchymal transition in colorectal cancer cells via the EGFR-independent pathway

Abstract

Abstract In the process of colonic epithelial carcinogenesis, the epithelial-mesenchymal transition may occur and bring metastatic ability and drug resistance. These events will affect patient outcomes and clinical treatment strategies. To this end, we investigated differentially expressed genes between several chemotherapy regimens in colon cancer cells through available transcriptomics datasets. We identified a member of the Rab family, RAB31, which is overexpressed after oxaliplatin treatment, while the other option is not (Irinotecan). We confirmed that RAB31 can enhance resistance to oxaliplatin in some overexpression models and that RAB31 has the ability to promote exocytosis and vesicle trafficking. Using shRNA as complementary models, we observed consistent trends when RAB31 function was discarded. Moreover, our evidence determined epithelial-mesenchymal transition (EMT)-related molecules responsive in the RAB31 bidirectional models, including CDH2, SNAI1, SNAI2 and TWIST1. The expression of RAB31 has an independent prognostic value in patients with colon cancer and is significantly positively correlated with mesenchymal markers. Furthermore, the interactome analysis selected RAB31 and AGR2 to form a direct protein interaction. This result differs from previous studies that did not rely on EGFR binding and signaling. Taken together, our study found that RAB31 can modulate oxaliplatin sensitivity and EMT status, which are additional chemotherapeutic strategies and independent prognostic factors for the treatment of colorectal cancer. Citation Format: Chi-Long Chen, Michael Hsiao. RAB31 interacts with AGR2 to respond to oxaliplatin resistance and epithelial-mesenchymal transition in colorectal cancer cells via the EGFR-independent pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2485.