Abstract 1520: RAB31 triggers oxaliplatin resistance in colorectal cancer via epithelial-mesenchymal transition

Abstract

Abstract Colorectal tumorigenesis during Epithelial-Mesenchymal transition (EMT) is associated with cancer metastasis and drug resistance. The small G-proteins family has been implicated in the regulation of cell cytoskeleton, cell movement, and vesicle transport. Small G-proteins family is divided into five main families. The Rab protein family is a member of the Ras superfamily of small G-proteins. We analyzed all probes of the Rab family members from microarray datasets and RNA-sequencing. We further calculated the EMT scores by using an algorithm. Our results showed that the RAB31 expression levels of the three probes are positively correlated with EMT score (Pearson rho=0.72, 0.71 and 0.68, respectively). Compared with other family members, RAB31 had most significantly value in colorectal cancer cell lines. We established several two-way model with cDNA and shRNAs of RAB31, respectively. Furthermore, we observed that the expression of epithelial type marker CDH1 was inhibited, and mesenchymal type markers SNAI1 and SNAI2 were upregulated in RAB31 overexpression models. Moreover, we found that the protein level of RAB31 was correlated with several clinicopathological parameters (N status, M status) and disease-free survival in tissue arrays through immunohistochemistry staining. According to The Cancer Genome Atlas Program (TCGA) and online meta-database, high RNA level of RAB31 was consistent in colorectal cancer (HR=1.38, n=466 and HR=1.29, n=482) and correlated with poor prognosis of patients. In addition, we identified that RAB31 may associated with IC50 of oxaliplatin and EGFR trafficking. We concluded that RAB31 regulates the sensitivity of oxaliplatin, an additional chemotherapy strategy and an independent prognostic factor for colorectal cancer. Citation Format: Chi-Long Chen, Yu-Chan Chang, Michael Hsiao. RAB31 triggers oxaliplatin resistance in colorectal cancer via epithelial-mesenchymal transition [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1520.