癌症转移是癌症相关死亡的主要原因，这凸显了了解其潜在机制的重要性。肝细胞癌（HCC）是一种高度恶性的癌症，被选为我们的研究模型。我们的目标是利用体外和体内选择策略开发高转移细胞系，并通过微阵列分析通过比较它们来识别关键的转移相关基因。我们的结果表明，高转移细胞系表现出比亲本细胞明显更强的侵袭能力。微阵列分析发现胞苷脱氨酶（CDA）是一种与全身化疗耐药相关的基因，是高转移细胞中过度表达的基因之一。癌症基因组图谱计划的数据分析显示，虽然 CDA 在 HCC 中表达下调，但 CDA 高表达的患者预后往往较差。细胞模型证实 CDA 过度表达可增强细胞迁移和侵袭，而 CDA 敲低则会抑制这些能力。通过研究参与上皮间质转化（EMT）的关键分子，我们发现 CDA 过表达会增加肌成束蛋白、N-钙粘蛋白、β-连环蛋白和 snail 的表达，同时减少 E-钙粘蛋白的表达。相反，CDA 敲低产生相反的结果。此外，我们发现CDA调节NF-κB信号传导，从而控制N-钙粘蛋白的表达，从而促进HCC细胞的侵袭能力。我们分离了高度转移的细胞并鉴定了潜在的HCC转移相关基因。 CDA通过NF-κB通路调节EMT来促进细胞侵袭。未来的研究有必要探索 CDA 作为预后和治疗决策生物标志物的潜力。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Cancer metastasis is the leading cause of cancer-related deaths, underscoring the importance of understanding its underlying mechanisms. Hepatocellular carcinoma (HCC), a highly malignant type of cancer, was selected as our research model.We aimed to develop high-metastatic cell lines using in vitro and in vivo selection strategies and identify critical metastasis-related genes through microarray analyses by comparing them with parental cells.Our results showed that the high-metastatic cell lines exhibited significantly stronger invasion abilities than parental cells. Microarray analyses identified cytidine deaminase (CDA), a gene associated with systemic chemotherapy resistance, as one of the overexpressed genes in the high-metastatic cells. Data analysis from The Cancer Genome Atlas Program revealed that while CDA is downregulated in HCC, patients with high CDA expression tend to have poorer prognoses. Cell models confirmed that CDA overexpression enhances cell migration and invasion, whereas CDA knockdown inhibits these abilities. Investigating the key molecules involved in the epithelial-mesenchymal transition (EMT), we found that CDA overexpression increases the expression of fascin, N-cadherin, β-catenin, and snail while decreasing E-cadherin expression. Conversely, CDA knockdown produced opposite results. Additionally, we discovered that CDA regulates NF-κB signaling, which controls the expression of N-cadherin, thereby promoting the invasion capability of HCC cells.We isolated highly metastatic cells and identified potential HCC metastasis-related genes. CDA promotes cell invasion by regulating EMT through the NF-κB pathway. Future studies are warranted to explore the potential of CDA as a biomarker for prognosis and therapeutic decision-making.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.