Abstract 3171: ARL2 is required for homologous recombination repair and colon cancer stem cell maintenance

Abstract

Abstract ARL2 is a small GTP binding protein mediates many cytosolic functions including localization of Ras, dynamics of microtubule and fission of mitochondria but its nuclear function is not well elucidated yet. Here we present the novel role of ARL2 in human cancer nucleus and cancer stem cells (CSC). The cancer tissue gene expression data in The Human Protein Atlas and The Cancer Genome Atlas showed possible pro-cancer and nuclear role of ARL2 in colon cancers. The single cell RNA seq analysis suggests its function in colon stem cells. The activation mutant of K-Ras harboring colon cancer cells expressed less ARL2 than the wild type cells but increased ARL2 expression in CSC spheres. The deprivation of ARL2 in colon cancer cell lines using RNAi preferentially eliminated the CSC spheres while it resulted in minimal impact on bulk cultured cell (BCC) numbers. Suppression of ARL2 halted the BCC at M phase as expected but did not change cell cycle in CSC spheres. However, it led to accumulation of a DNA double strand break marker and apoptosis only in CSC spheres which suggest that ARL2’s requirement for double strand DNA break repair in CSC. Out of 6 somatic RAD51 family genes which all mediate the critical early events of homologous recombination repair (HRR), 5 showed significant and positive association with ARL2 in gene expression in human colon cancer tissue suggesting functional link between ARL2 and HRR. Indeed, ARL2 was required for HRR when double strand DNA breaks were induced. These data collectively showed that ARL2 may contribute to the HRR in the nucleus and the ARL2 mediated HRR is more critical for colon CSC survival. Citation Format: Seok Gyeong Choi, Hani Lee, Sojung Ha, Sukjoon Yoon, Woo-Young Kim. ARL2 is required for homologous recombination repair and colon cancer stem cell maintenance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3171.