ONCOmmunity

ZEB1 promotes epithelial-mesenchymal transition in cervical cancer metastasis.

By: Jing Ran, Dian-Liang Lin, Rong-Feng Wu, Qiong-Hua Chen, Hui-Ping Huang, Na-Xuan Qiu, Song Quan

Reproductive Medicine Center, Nan Fang Hospital, Southern Medical University, Guangzhou, People's Republic of China; Department of Gynecology and Obstetrics, First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
2015-1-20; doi: 10.1016/j.fertnstert.2015.03.016

Abstract

Objective

To investigate role of Zinc finger E-box binding homeobox 1 (ZEB1) in cervical cancer tissue (squamous cell carcinoma, SCC).

Design

Exploratory study.

Setting

University hospital.

Patient(s)

Sixty patients with SCC, including stage CINIII (n = 10), IB1 (n = 10), IB2 (n = 10), IIA1 (n = 10), IIA2 (n = 10), and IIB (n = 10) were studied.

Intervention(s)

Caski cells were transfected with recombinant shZEB1 lentivirus or shCtrl lentivirus to generate stable ZEB1-knockdown Caski cells.

Main

ZEB1 expression was analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry in cervical cancer tissues. ZEB1 expression in Caski cells was down-regulated by short-hairpin RNA (shRNA) interference, and changes in ZEB1 expression corresponded with changes in the proliferation and migratory ability of Caski cells.

Result(s)

Quantitative real-time polymerase chain reaction and immunohistochemistry results revealed that ZEB1 expression and the ratio of Vimentin to E-cadherin were high in 27 of 50 SCC patients and correlated with advanced International Federation of Gynecology and Obstetrics stage, tumor size >4 cm, and parametrial invasion. However, the expression of ZEB1 in cervical cancer tissue was independent of age and SCC antigen level. Transfection of ZEB1 shRNA in Caski cells significantly decreased the messenger RNA and protein expression of ZEB1, parallel with increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal marker Vimentin. Furthermore, the proliferation and migratory ability of Caski cells were significantly lower in the transfected group than in the nontransfected control group.

Conclusion(s)

Down-regulation of ZEB1 expression may protect the invasive front of the tumors from converting to a mesenchymal phenotype by reducing the proliferation and motility of cervical cancer cells, suggesting that ZEB1 might be a potential therapeutic target for SCC.