Dou Chunqing, Jin Xin, Sun Liyuan, Zhang Bao, Han Mingming, Li Tao
Cancer Biomark. 2017 Jul 4;19(4):447-454. doi: 10.3233/CBM-170139.
The transcription factor FOXF2 is reported to be down-regulated in HCC. Its deficiency is correlated with shorter disease-free survival and overall survival of HCC patients; however, the mechanism remains to be elucidated.
In this study, we performed qRT-PCR and western blotting to confirm the down-regulated FOXF2 in HCC tissue and cell lines. Then the HCC cell line Huh7 transduced with FOXF2 shRNA was adopted in a series of in vitro and in vivo assays to evaluate the cell phenotype change, migration, invasion, proliferation, colonization of circulating cell and the formation of metastatic nodules.
We found that FOXF2 was down-regulated in HCC tissues and cell lines. FOXF2 deficiency in Huh7 cells increased E-cadherin and decreased Vimentin. The down-regulation of FOXF2 impeded HCC cell migration and invasion capacity, but promoted the proliferation of HCC cells and the growth of subcutaneous tumors in nude mice, which indicated a mesenchymal-to-epithelial phenotypic change in Huh7 cells. FOXF2 deficiency enhanced the colonization of circulating HCC cell, thus promoted the formation of metastatic nodules.
FOXF2 deficiency induced mesenchymal-epithelial transition (MET) in Huh7 cell which might facilitate the colonization of circulating tumor cells and the formation of metastasis.
据报道，转录因子FOXF2在肝癌中表达下调。其缺陷与肝癌患者较短的无病生存期和总生存期相关；然而，其机制仍有待阐明。
在本研究中，我们进行了qRT-PCR和蛋白质印迹分析，以证实肝癌组织和细胞系中FOXF2表达下调。然后，采用转导了FOXF2 shRNA的肝癌细胞系Huh7进行一系列体外和体内试验，以评估细胞表型变化、迁移、侵袭、增殖、循环细胞定植及转移瘤结节形成情况。
我们发现FOXF2在肝癌组织和细胞系中表达下调。Huh7细胞中FOXF2缺陷导致E-钙黏蛋白增加，波形蛋白减少。FOXF2下调阻碍了肝癌细胞的迁移和侵袭能力，但促进了肝癌细胞的增殖以及裸鼠皮下肿瘤的生长，这表明Huh7细胞发生了间充质向上皮的表型转变。FOXF2缺陷增强了循环肝癌细胞的定植，从而促进了转移瘤结节的形成。
FOXF2缺陷诱导Huh7细胞发生间充质-上皮转化（MET），这可能促进循环肿瘤细胞的定植和转移形成。
