Department of Cardiothoracic Surgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
Thorac Cancer. 2019 Jan;10(1):24-32. doi: 10.1111/1759-7714.12893. Epub 2018 Nov 15.
Capn4 and ZEB1 play important roles in the metastasis of several types of cancer. However, the roles and relationship of Capn4 and ZEB1 in esophageal squamous cell carcinoma (ESCC) remain unclear.
ESCC tumor tissues and corresponding normal esophageal epithelial tissues were obtained from 86 patients undergoing resection surgery at the Department of General Surgery, First Affiliated Hospital of Chinese PLA General Hospital from 2012 to 2017. Cell migration and invasion were examined via quantitative real-time PCR and Western blot assay.
Our results indicate that both Capn4 and ZEB1 are significantly upregulated in ESCC tissues compared to corresponding adjacent tissues, and a positive correlation between expression and associated malignant characteristics was found. Silencing of Capn4 expression markedly inhibited ESCC invasion and metastasis in vitro and in vivo, and was accompanied by decreased ZEB1 expression. Furthermore, the anti-metastasis role of Capn4 silencing was reversed by ZEB1 overexpression, whereas knockdown of ZEB1 decreased ESCC metastasis driven by the upregulation of Capn4. Mechanistically, Capn4 regulated ZEB1 expression via activation of the Wnt/β-catenin signaling pathway in ESCC cells.
Overall, our results show that enhanced Capn4 expression activates the Wnt/β-catenin signaling pathway, resulting in increased ZEB1 expression and the promotion of ESCC cell metastasis.
Capn4 和 ZEB1 在多种类型的癌症转移中发挥重要作用。然而，Capn4 和 ZEB1 在食管鳞状细胞癌（ESCC）中的作用和关系尚不清楚。
本研究收集了 2012 年至 2017 年期间在中国人民解放军总医院普通外科接受手术切除的 86 例 ESCC 患者的肿瘤组织和相应的正常食管上皮组织。通过实时定量 PCR 和 Western blot 检测细胞迁移和侵袭。
我们的结果表明，Capn4 和 ZEB1 在 ESCC 组织中均明显上调，与相应的相邻组织相比，表达水平与相关恶性特征呈正相关。Capn4 表达的沉默显著抑制了 ESCC 在体外和体内的侵袭和转移，同时伴随着 ZEB1 表达的降低。此外，Capn4 沉默的抗转移作用被 ZEB1 的过表达所逆转，而 ZEB1 的敲低则降低了由 Capn4 上调驱动的 ESCC 转移。机制上，Capn4 通过激活 ESCC 细胞中的 Wnt/β-catenin 信号通路来调节 ZEB1 的表达。
总的来说，我们的研究结果表明，增强的 Capn4 表达激活了 Wnt/β-catenin 信号通路，导致 ZEB1 表达增加，促进了 ESCC 细胞的转移。
