Abstract 5440: TM4SF1 maintains cancer stemness in cholangiocarcinoma

Abstract

Abstract Cholangiocarcinoma (CCA) is an aggressive liver malignancy with increased incidence globally but poor prognosis. Cancer stemness plays critical roles on tumor initiation, recurrence, and resistance to therapy. However, the mechanism of stemness maintenance in CCA has been less explored. Previously, we have reported TM4SF1 is associated with poor survival in CCA and high expression of TM4SF1 tends to promote tumorigenesis. In this study, we found that the expression of TM4SF1 gene is upregulated in tumor tissues compared to adjacent normal tissues in CCA based on bulk RNA sequencing dataset from The Cancer Genome Atlas (TGCA) CCA cohort. There is a positive correlation between the expression of TM4SF1 and stemness genes, ITGB3, SOX9, ALDH1A3, and ITGB1. Interestingly, knockdown of TM4SF1 with siRNA in CCA cell line HuCCT-1 cells demonstrated a decrease in expression of cancer stem cell surface markers, CD24 and Prom1. Furthermore, with a CRISPR-based lentivirus construct to knockdown TM4SF1 gene in HuCCT-1 cells in vitro, we found that spheroid formation in TM4SF1 knockdown was attenuated in comparison to TM4SF1 wild type. In addition, the results from flow cytometry and RT-PCR showed a corresponding decrease in CD24 and CD133 expression with TM4SF1 knockdown when comparing to TM4SF1 wild type. In conclusion, TM4SF1 is associated with the stemness of CCA and could be a therapeutic target for CCA therapy to overcome therapy resistance in future. Citation Format: Xiao Bin Zhu, Jihye Golino, Xin Wang, Changqing Xie. TM4SF1 maintains cancer stemness in cholangiocarcinoma [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 5440.