Yang KanKan, Jiang LinHua, Hu You, Yu Jing, Chen HenFeng, Yao YiZhou, Zhu XinGuo
Department of General Surgery, The First Affiliated Hospital of Soochow University, 215006, Suzhou, Jiangsu Province, China.
Department of Laparoscopic Surgery, The First Affiliated Hospital of Soochow University, 215006, Suzhou, Jiangsu Province, China.
J Exp Clin Cancer Res. 2015 May 3;34(1):40. doi: 10.1186/s13046-015-0158-1.
The Forkhead box M1 (FOXM1) is an oncogenic transcription factor and plays a significant role in cell EMT, proliferation, metastasis in a multitude of human solid tumors including colorectal cancer (CRC). However, the underlying molecular mechanisms by which FoxM1 contributes to epithelial-to-mesenchymal (EMT) and metastasis have not been fully elucidated in CRC.
In our study, we investigated FOXM1 protein expression in 87 CRC tissue specimens, invasive lymph nodes and adjacent paired normal colorectal tissues by immunohistochemical analysis. Then we transfected FOXM1 specific shRNA into SW620 cells to examine effect of FOXM1 on proliferation, colony formation, migration and invasion in vitro. Western blotting and real-time PCR were used to detect the protein and mRNA expression of FOXM1 and EMT-related markers.
FOXM1 was overexpressed in CRC tissues, invasive lymph nodes and CRC cell lines. FoxM1 overexpression was significantly associated with lymph node metastasis (P < 0.001), and tumor recurrence (P < 0.001). Moreover, downregulation of FOXM1 in SW620 cells by shRNA approach inhibited cell growth, clonogenicity, migration and invasion in vitro. In addition, decreased FOXM1 expression in SW620 cells reversed the acquisition of EMT phenotype by up-regulating E-cadherin, as well as reduction Vimentin and Snail expressions at protein and mRNA levels.
FOXM1 may regulate CRC cells metastasis through EMT program and FOXM1 may be a potential target for treatment of CRC.
叉头框M1（FOXM1）是一种致癌转录因子，在包括结直肠癌（CRC）在内的多种人类实体瘤的细胞上皮-间质转化（EMT）、增殖和转移中发挥重要作用。然而，在结直肠癌中，FoxM1促进上皮-间质转化（EMT）和转移的潜在分子机制尚未完全阐明。
在我们的研究中，我们通过免疫组织化学分析调查了87例结直肠癌组织标本、侵袭性淋巴结和相邻配对正常结直肠组织中FOXM1蛋白的表达。然后我们将FOXM1特异性短发夹RNA转染到SW620细胞中，以检测FOXM1对体外增殖、集落形成、迁移和侵袭的影响。采用蛋白质免疫印迹法和实时定量PCR检测FOXM1和EMT相关标志物的蛋白质和mRNA表达。
FOXM1在结直肠癌组织、侵袭性淋巴结和结直肠癌细胞系中过表达。FoxM1过表达与淋巴结转移（P < 0.001）和肿瘤复发（P < 0.001）显著相关。此外，通过短发夹RNA方法下调SW620细胞中的FOXM1可抑制细胞在体外的生长、克隆形成、迁移和侵袭。此外，SW620细胞中FOXM1表达的降低通过上调E-钙黏蛋白，以及在蛋白质和mRNA水平上降低波形蛋白和Snail的表达，逆转了EMT表型的获得。
FOXM1可能通过EMT程序调节结直肠癌细胞的转移，并且FOXM1可能是结直肠癌治疗的潜在靶点。
