Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Acta Biochim Biophys Sin (Shanghai). 2020 Dec 11;52(11):1247-1256. doi: 10.1093/abbs/gmaa117.
Intrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. The overexpression of COUP-TFII has been observed in several types of malignancies. However, its role in ICC progression remains unclear. In this study, we found that the protein level of COUP-TFII was increased, but the mRNA level was unchanged in ICC tissues. High protein expression was positively associated with tumor size, lymph node metastasis, and poor prognosis in ICC patients. Furthermore, the overexpression of COUP-TFII promoted the proliferation, migration, and invasion of ICC cells in vitro and enhanced tumor growth and metastasis in nude mouse models. Mechanistic studies revealed that COUP-TFII induced epithelial-to-mesenchymal transition in ICC cells by upregulating Snail expression. Moreover, the activation of PI3K/AKT signaling led to the upregulation of COUP-TFII protein expression in ICC. Together, these findings indicate that COUP-TFII promotes epithelial-to-mesenchymal transition and metastasis in ICC and suggest that this protein is a potential target for adjuvant therapy for these patients.
肝内胆管癌（ICC）起源于肝内胆管的胆管细胞，是第二大常见的肝癌类型。COUP-TFII 的过表达已在几种类型的恶性肿瘤中观察到。然而，其在 ICC 进展中的作用尚不清楚。在这项研究中，我们发现 COUP-TFII 的蛋白水平在 ICC 组织中升高，但 mRNA 水平不变。COUP-TFII 的高表达与 ICC 患者的肿瘤大小、淋巴结转移和预后不良呈正相关。此外，COUP-TFII 的过表达促进了 ICC 细胞在体外的增殖、迁移和侵袭，并增强了裸鼠模型中的肿瘤生长和转移。机制研究表明，COUP-TFII 通过上调 Snail 的表达诱导 ICC 细胞发生上皮间质转化。此外，PI3K/AKT 信号的激活导致 ICC 中 COUP-TFII 蛋白表达的上调。总之，这些发现表明 COUP-TFII 促进了 ICC 中的上皮间质转化和转移，并提示该蛋白可能是这些患者辅助治疗的潜在靶点。
