Identification of odontogenic ameloblast associated as a novel target gene of the Wnt/β‐catenin signaling pathway

• DOI: 10.1111/cas.15657
• Publication Date: 2022-11-16T09:53:30Z
• Authors: Kiyoshi Yamaguchi; Chiaki Horie; Kiyoko Takane; Tsuneo Ikenoue; Saya Nakagawa; Yumiko Isobe; Yasunori Ota; Tetsuo Ushiku; Mariko Tanaka; Jun Fujishiro; Noriko Hoshino; Atsuhiro Arisue; Satoshi Nishizuka; Susumu Aikou; Dai Shida; Yoichi Furukawa
• Keywords: 0301 basic medicine; 0303 health sciences; Carcinoma, Hepatocellular; Liver Neoplasms; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Cell Line, Tumor; Ameloblasts; Humans; ORIGINAL ARTICLES; Wnt Signaling Pathway; beta Catenin; Cell Proliferation

AbstractThe Wnt/β‐catenin signaling pathway plays a key role in development and carcinogenesis. Although some target genes of this signaling have been identified in various tissues and neoplasms, the comprehensive understanding of the target genes and their roles in the development of human cancer, including hepatoma and colorectal cancer remain to be fully elucidated. In this study, we searched for genes regulated by the Wnt signaling in liver cancer using HuH‐7 hepatoma cells. A comparison of the expression profiles between cells expressing an active form of mutant β‐catenin and cells expressing enhanced green fluorescent protein (EGFP) identified seven genes upregulated by the mutant β‐catenin gene (CTNNB1). Among the seven genes, we focused in this study on ODAM, odontogenic, ameloblast associated, as a novel target gene. Interestingly, its expression was frequently upregulated in hepatocellular carcinoma, colorectal adenocarcinoma, and hepatoblastoma. We additionally identified a distant enhancer region that was associated with the β‐catenin/TCF7L2 complex. Further analyses revealed that ODAM plays an important role in the regulation of the cell cycle, DNA synthesis, and cell proliferation. These data may be useful for clarification of the main molecular mechanism(s) underlying these cancers.