C端口腺苷酸酰化样蛋白(CTEN)是一种常见于聚焦粘附点细胞质侧的腺苷酸酰化样蛋白，主要参与细胞黏附和迁移。在多种癌症中发现了CTEN表达升高和核积累，与恶性行为相关。然而，核CTEN的功能仍不清楚。在本研究中，我们首次报告了核CTEN与染色质DNA相互作用，并且占据多个基因启动位点附近的区域。CTEN的mRNA表达水平与其一个潜在靶基因细胞分裂周期蛋白27(CDC27)在临床结肠癌数据集中呈正相关，提示CTEN可能在调控CDC27基因表达方面具有作用。此外，我们证明了CTEN被招募到CDC27基因启动区域上，并且当CTEN被降调时，CDC27的mRNA表达和启动子活性都降低。此外，我们发现通过过表达CTEN与核定位信号相融合，增强HCT116细胞内CTEN的核积累会提高CDC27转录水平和启动子活性。增强核定位的CTEN也显著促进细胞迁移，并且当CDC27被沉默时迁移能力被压制。这些结果表明核CTEN通过CDC27转录调控并促进细胞迁移。我们的研究结果提供了CTEN在细胞核内作为DNA关联蛋白和转录调节因子的新见解，从而影响癌细胞迁移。 ©2022. 该作者根据Navarra大学授予的独家许可证。

C-terminal tensin-like (CTEN) is a tensin family protein typically localized to the cytoplasmic side of focal adhesions, and primarily contributes to cell adhesion and migration. Elevated expression and nuclear accumulation of CTEN have been reported in several types of cancers and found to be associated with malignant behaviors. However, the function of nuclear CTEN remains elusive. In this study, we report for the first time that nuclear CTEN associates with chromatin DNA and occupies the region proximal to the transcription start site in several genes. The mRNA expression level of CTEN positively correlates with that of one of its putative target genes, cell division cycle protein 27 (CDC27), in a clinical colorectal cancer dataset, suggesting that CTEN may play a role in the regulation of CDC27 gene expression. Furthermore, we demonstrated that CTEN is recruited to the promoter region of the CDC27 gene and that the mRNA expression and promoter activity of CDC27 are both reduced when CTEN is downregulated. In addition, we found that enhanced nuclear accumulation of CTEN in HCT116 cells by overexpression of CTEN fused with nuclear localization signals increases CDC27 transcript levels and promoter activity. The increased nuclear-localized CTEN also significantly promotes cell migration, and the migratory ability is suppressed when CDC27 is knocked down. These results demonstrate that nuclear CTEN regulates CDC27 expression transcriptionally and promotes cell migration through CDC27. Our findings provide new insights into CTEN moonlighting in the nucleus as a DNA-associated protein and transcriptional regulator involved in modulating cancer cell migration.© 2022. The Author(s) under exclusive licence to University of Navarra.