Fan Qiong, Qiu Mei-Ting, Zhu Zhu, Zhou Jin-Hua, Chen Limo, Zhou Ye, Gu Wei, Wang Li-Hua, Li Zhu-Nan, Xu Ying, Cheng Wei-Wei, Wu Dan, Bao Wei
Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, P.R. China.
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Oncol Rep. 2015 Oct;34(4):1787-94. doi: 10.3892/or.2015.4143. Epub 2015 Jul 22.
Epithelial-mesenchymal transition (EMT) is associated with the metastasis and poor prognosis of cervical cancer. However, the underlying mechanisms are poorly defined. In the present study, we investigated whether Twist plays a direct role in human cervical cancer using immunohistochemical and western blot analyses. Immunohistochemical analysis revealed that Twist is highly expressed in cervical cancer, which correlates with poor tumor pathological differentiation or lymph node metastasis (P<0.05). Depletion of Twist by stable shRNA-mediated knockdown decreased the migratory ability of cancer cell lines in vitro. Suppression or overexpression of Twist also resulted in an altered expression of the molecular mediators of EMT. Furthermore, exogenous TGF-β promoted EMT by upregulating the expression of Twist through the TGF-β/Smad3 pathway, and this effect was eliminated by Twist depletion in cancer cells as demonstrated in the in vitro study. The use of in vivo models revealed a decreased tumor proliferation potential in Twist-depleted cancer cells. The results suggested a novel function for Twist in the promotion of EMT via TGF-β/Smad3 signaling pathway. Thus, Twist constitutes a potential therapeutic target in human cervical cancer.
上皮-间质转化（EMT）与宫颈癌的转移及不良预后相关。然而，其潜在机制尚不清楚。在本研究中，我们运用免疫组织化学和蛋白质印迹分析，探究Twist在人类宫颈癌中是否发挥直接作用。免疫组织化学分析显示，Twist在宫颈癌中高表达，这与肿瘤病理分化差或淋巴结转移相关（P<0.05）。通过稳定的短发夹RNA（shRNA）介导的敲低使Twist缺失，可降低癌细胞系在体外的迁移能力。Twist的抑制或过表达也导致EMT分子介质表达的改变。此外，体外研究表明，外源性转化生长因子-β（TGF-β）通过TGF-β/ Smad3信号通路上调Twist的表达来促进EMT，而癌细胞中Twist缺失可消除这种作用。体内模型研究显示，Twist缺失的癌细胞肿瘤增殖潜能降低。结果表明，Twist通过TGF-β/ Smad3信号通路促进EMT具有新功能。因此，Twist构成人类宫颈癌潜在的治疗靶点。
