Department of Oncology, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China.
Department of Interventional Medical Center, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China.
Mol Med Rep. 2017 Oct;16(4):5181-5188. doi: 10.3892/mmr.2017.7223. Epub 2017 Aug 10.
Forkhead box protein M1 (FoxM1) is aberrantly expressed in several types of human malignancy, and serves an important role in tumor metastasis. Epithelial‑mesenchymal transition (EMT) of cancer cells has been associated cancer metastasis; however, the implication of FoxM1 in EMT and its putative roles in the regulation of cancer metastasis remain to be elucidated. In the present study, the expression of FoxM1, Snai1 and E‑cadherin in hepatocellular carcinoma (HCC) cell lines with various metastatic potentials, and in normal liver cells, was investigated using western blot analysis and reverse transcription‑quantitative polymerase chain reaction. The effects of FoxM1 on the invasive and migratory capabilities of HCC cells were evaluated using wound healing and Transwell migration assays. The present results demonstrated that FoxM1 expression was significantly upregulated in HCC cells compared with in normal hepatocytes (P<0.05). In addition, FoxM1 expression was significantly increased in MHCC‑LM3 cells, characterized by higher metastatic potential, compared with in SMMC‑7721 cells, which have a lower metastatic potential. Furthermore, overexpression of FoxM1 was demonstrated to be negatively correlated with E‑cadherin (P<0.05) and positively associated with Snai1 (P<0.05) expression. These observations suggested that FoxM1 may enhance the invasion and migration of cancer cells, and thus promotes their EMT, in a mechanism that may involve the regulation of Snai1. Therefore, it may be hypothesized that FoxM1 has potential as a novel diagnostic marker and therapeutic target for the treatment of patients with HCC.
叉头框蛋白 M1（FoxM1）在几种人类恶性肿瘤中异常表达，在肿瘤转移中发挥重要作用。癌细胞的上皮-间充质转化（EMT）与癌症转移有关；然而，FoxM1 在 EMT 中的作用及其在调节癌症转移中的潜在作用仍有待阐明。在本研究中，通过 Western blot 分析和逆转录-定量聚合酶链反应，研究了具有不同转移潜能的肝癌细胞系和正常肝细胞中 FoxM1、Snai1 和 E-钙黏蛋白的表达。通过划痕愈合和 Transwell 迁移实验评估了 FoxM1 对肝癌细胞侵袭和迁移能力的影响。本研究结果表明，与正常肝细胞相比，肝癌细胞中 FoxM1 的表达显著上调（P<0.05）。此外，在具有较高转移潜能的 MHCC-LM3 细胞中，FoxM1 的表达明显高于具有较低转移潜能的 SMMC-7721 细胞。此外，FoxM1 的过表达与 E-钙黏蛋白呈负相关（P<0.05），与 Snai1 呈正相关（P<0.05）。这些观察结果表明，FoxM1 可能通过调节 Snai1 增强癌细胞的侵袭和迁移，从而促进 EMT。因此，可以假设 FoxM1 可能作为一种新的诊断标志物和治疗靶点，用于治疗 HCC 患者。
