Abstract 1559: IKZF1 plays a crucial role in the spread of melanoma

Abstract

Abstract Melanoma is one of the most fatal type of skin cancer. If melanoma has spread to distant sites, it is refractory to existing therapies with the 5-year survival rate declining to 17%. Metastasis remains as the main barrier to successful therapy, persisting as the main cause of cancer-related death. Thus, understanding metastasis mechanism is vital. First, we confirmed that IKZF1 gene was more increased in circulating tumor cells than primary tumor cells. Using GFP+ B16F10, we generated an orthotopic melanoma mouse model and isolated GFP+ tumor cells of primary footpad, blood, and lung. In single cell RNA sequencing, IKZF1, IRF8, NFE2 genes were more upregulated in circulating tumor cells than primary tumor cells. We also found these correlations in human melanoma cell line orthotopic mouse model and Braf/Pten mouse model. Next, we conduct intervention study to find causality in IKZF1 and metastasis. IKZF1 KO led to fewer CTCs and IKZF1 inhibitor, lenalidomide, reduced metastasis in mice. Collectively, we demonstrate that IKZF1 could contribute the formation of CTC and IKZF1 could be a target for metastasis treatment. Citation Format: Jongwook Oh, Dong Ki Lee, Soyeon Lee, Hyun Woo Park, Heon Yung Gee. IKZF1 plays a crucial role in the spread of melanoma [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 1559.