Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
Cancer Sci. 2013 Nov;104(11):1427-32. doi: 10.1111/cas.12249. Epub 2013 Sep 15.
Extrahepatic cholangiocarcinoma (EHCC) is a cancer with a poor prognosis, and the postoperative survival of patients depends on the existence of invasion and metastasis. The epithelial-to-mesenchymal transition (EMT) is an important step in EHCC invasion and metastasis. Forkhead box protein C2 (FOXC2) is a transcription factor that has been reported to induce the EMT. Therefore we examined the correlation between FOXC2 expression and clinical pathological factors, and analysed the function of FOXC2. The expression of FOXC2 in 77 EHCC cases was investigated by immunohistochemical staining, and the relationship between FOXC2 expression and clinicopathological factor was assessed. Knockdown by small interfering RNA (siRNA) was performed to determine the roles of FOXC2 in EHCC cell line. FOXC2 expression correlated with lymph node metastasis (P = 0.0205). Patients in the high FOXC2 expression group had a poorer prognosis than the patients in the low FOXC2 expression group. Moreover, FOXC2 knockdown inhibited cell motility and invasion, and decreased the expression of EMT markers (N-cadherin, and matrix metalloproteinase (MMP) -2) and Angiopietin-2 (Ang-2). The EMT inducer FOXC2 contributes to a poor prognosis and cancer progression. FOXC2 may be a promising molecular target for regulating EHCC metastasis.
肝外胆管癌（EHCC）预后较差，患者的术后生存取决于是否存在侵袭和转移。上皮间质转化（EMT）是 EHCC 侵袭和转移的重要步骤。叉头框蛋白 C2（FOXC2）是一种转录因子，已被报道可诱导 EMT。因此，我们研究了 FOXC2 表达与临床病理因素之间的相关性，并分析了 FOXC2 的功能。通过免疫组织化学染色检测 77 例 EHCC 病例中 FOXC2 的表达，评估 FOXC2 表达与临床病理因素之间的关系。通过小干扰 RNA（siRNA）敲低来确定 FOXC2 在 EHCC 细胞系中的作用。FOXC2 表达与淋巴结转移相关（P=0.0205）。FOXC2 高表达组患者的预后较 FOXC2 低表达组差。此外，FOXC2 敲低抑制了细胞迁移和侵袭，并降低了 EMT 标志物（N-钙黏蛋白和基质金属蛋白酶（MMP）-2）和血管生成素-2（Ang-2）的表达。EMT 诱导因子 FOXC2 导致预后不良和癌症进展。FOXC2 可能是调节 EHCC 转移的有前途的分子靶标。
