结直肠癌（CRC）是全世界死亡率最高的癌症之一，各种研究报告了CRC的发生。特别是，Wnt/β-catenin 通路被认为是 CRC 进展的主要因素，β-catenin 参与其下游靶基因的表达。我们通过银染色寻找 TCOF1，以确定 β-连环蛋白的新结合伴侣，并研究该基因在 CRC 中的作用。 Treacle 核糖体生物发生因子 1 (TCOF1) 是一种调节核糖体 DNA (rDNA) 转录的核仁蛋白。关于 TCOF1 突变和缺陷的遗传学研究有很多报道，但其在 CRC 中的功能仍不清楚。我们证明了 TCOF1 和 β-连环蛋白在包含 101 个个体 CRC 和 17 个相邻正常样本的组织微阵列 (TMA) 中的表达。此外，还检查了 TCOF1 敲低或过表达对增殖、集落形成测定、蛋白质印迹和定量实时 PCR (qRT-PCR) 的影响。 TCOF1 敲低或过表达可调节细胞增殖约三倍以及 β-连环蛋白、细胞周期蛋白 D1 表达水平的磷酸化。此外，我们通过泛素化实验发现TCOF1调节β-catenin稳定性的机制参与了蛋白酶体的降解。最后，我们证实了 TCOF1 与端锚聚合酶抑制剂 NVP-TNKS656 的相互作用，后者通过体外和体内破坏 β-连环蛋白的稳定性。总的来说，这项研究表明，TCOF1 和 β-catenin 是肿瘤进展的危险因素，存在显着相关性。通过调节 TCOF1 表达实现 β-连环蛋白的稳定性可能是治疗 CRC 的潜在策略。© 2023。作者获得 Springer Science Business Media, LLC（Springer Nature 旗下子公司）的独家许可。

Colorectal cancer (CRC) is one of the highest mortality rates worldwide, and various studies reported to the occurrence of CRC. In particular, the Wnt/β-catenin pathway is known to be a major factor in the progression of CRC and β-catenin involved in the expression of its downstream target genes. We searched for TCOF1 through sliver staining to identify a new binding partner for β-catenin and to investigate the role of the gene involved in CRC. Treacle Ribosome Biogenesis Factor 1 (TCOF1) is a nucleolar protein that regulates the transcription of ribosomal DNA (rDNA). There are many reports of genetic studies on TCOF1 mutations and defects, but its function in CRC remains unknown. We demonstrated that TCOF1 and β-catenin expression in tissue microarray (TMA) containing 101 individual CRC and 17 adjacent normal samples. Additionally, the effects of TCOF1 knockdown or overexpression were examined proliferation, colony formation assay, western blot, and quantitative real-time PCR (qRT-PCR). TCOF1 knockdown or overexpression regulates cell proliferation about three-fold and the phosphorylation of β-catenin, cyclin D1 expression levels. Besides, we discovered the mechanism through which TCOF1 regulates the stability of β-catenin was involved in degradation through proteasome using ubiquitination assay. Finally, we confirmed the interaction of TCOF1 with the tankyrase inhibitor NVP-TNKS656, which destabilizes β-catenin through in vitro and in vivo. Collectively, this study shows that significantly correlation was observed that TCOF1 and β-catenin were risk factor for tumor progression. The stability of β-catenin via regulating TCOF1 expression could be a potential strategy for therapeutic with CRC.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.