Cell division cycle associated 7 (CDCA7) is a copy number amplification gene that contributes to the metastasis and invasion of tumors, including esophageal squamous cell carcinoma (ESCC). This present study aimed at clarifying whether high expression of CDCA7 promotes the metastasis and invasion of ESCC cell lines and exploring the underlying mechanisms implicated in epithelial–mesenchymal transition (EMT) of ESCC. The role of CDCA7 in the regulation of ESCC metastasis and invasion was evaluated using ESCC cell lines. Expression of EMT-related markers including E-cadherin, N-cadherin, Vimentin, Snail, and Slug, transforming growth factor β (TGF-β) signaling pathway including Smad2/3, p-Smad2/3, Smad4, and Smad7 were detected in CDCA7 knockdown and overexpressed cell lines. Dual-luciferase reporter assay and rescue assay were used to explore the underlying mechanisms that CDCA7 contributed to the metastasis and invasion of ESCC. High CDCA7 expression significantly promoted the metastasis and invasion of ESCC cell lines both in vivo and in vitro. Additionally, the expression of CDCA7 positively correlated with the expression of N-cadherin, Vimentin, Snail, Slug, TGF-β signaling pathway and negatively correlated with the expression of E-cadherin. Furthermore, CDCA7 transcriptionally regulated the expression of Smad4 and Smad7. Knockdown of CDCA7 inhibited the TGF-β signaling pathway and therefore inhibited EMT. Our data indicated that CDCA7 was heavily involved in EMT by regulating the expression of Smad4 and Smad7 in TGF-β signaling pathway. CDCA7 might be a new therapeutic target in the suppression of metastasis and invasion of ESCC.

中文翻译：

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CDCA7 通过转录调节 ESCC 中的 Smad4/Smad7 促进 TGF-β 诱导的上皮-间质转化

细胞分裂周期相关 7 ( CDCA7 ) 是一种拷贝数扩增基因，有助于肿瘤的转移和侵袭，包括食管鳞状细胞癌 (ESCC)。本研究旨在阐明 CDCA7 的高表达是否促进 ESCC 细胞系的转移和侵袭，并探索与 ESCC 上皮 - 间质转化（EMT）有关的潜在机制。使用 ESCC 细胞系评估 CDCA7 在调节 ESCC 转移和侵袭中的作用。检测EMT相关标志物包括E-cadherin、N-cadherin、Vimentin、Snail和Slug的表达，转化生长因子β（TGF-β）信号通路包括Smad2/3、p-Smad2/3、Smad4和Smad7在CDCA7击倒和过表达的细胞系。双荧光素酶报告实验和拯救实验被用来探索CDCA7促进食管鳞癌转移和侵袭的潜在机制。CDCA7 的高表达显着促进了 ESCC 细胞系在体内和体外的转移和侵袭。此外，CDCA7的表达与N-cadherin、Vimentin、Snail、Slug、TGF-β信号通路的表达呈正相关，与E-cadherin的表达呈负相关。此外，CDCA7 转录调节 Smad4 和 Smad7 的表达。CDCA7的击倒抑制 TGF-β 信号通路，从而抑制 EMT。我们的数据表明 CDCA7 通过调节 TGF-β 信号通路中 Smad4 和 Smad7 的表达而大量参与 EMT。CDCA7可能是抑制ESCC转移和侵袭的新治疗靶点。