CLDN1 expression in cervical cancer cells is related to tumor invasion and metastasis
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Wei-na Zhang1,2,*, Wei Li1,*, Xiao-li Wang1, Zheng Hu1, Da Zhu1, Wen-cheng Ding1, Dan Liu1, Ke-zhen Li1, Ding Ma1, Hui Wang1
1Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
2Department of Gynecology, Qingdao Municipal Hospital, Qingdao, Shandong 266000, P.R. China
*These authors have contributed equally to this work
Ding Ma, email: firstname.lastname@example.org
Hui Wang, email: email@example.com
Keywords: cervical cancer, CLDN1, array CGH, EMT
Received: August 29, 2016 Accepted: November 07, 2016 Published: December 10, 2016
Even though infection with human papillomaviruses (HPV) is very important, it is not the sole cause of cervical cancer. Because it is known that genetic variations that result from HPV infection are probably the most important causes of cervical cancer, we used human whole genome array comparative genomic hybridization to detect the copy number variations of genes in cervical squamous cell carcinoma. The results of the array were validated by PCR, FISH and immunohistochemistry. We find that the copy number and protein expression of claudin-1 (CLDN1) increase with the progression of cervical cancer. The strong positive staining of CLDN1 in the cervical lymph node metastasis group received a significantly higher score than the staining in the group with no lymph node metastasis of cervical cancer tissues. The overexpression of CLDN1 in SiHa cells can increase anti-apoptosis ability and promote invasive ability of these cells accompanied by a decrease in expression of the epithelial marker E-cadherin as well as an increase in the expression of the mesenchymal marker vimentin. CLDN1 induces the epithelial-mesenchymal transition (EMT) through its interaction with SNAI1. Furthermore, we demonstrate that CLDN1 overexpression has significant effects on the growth and metastasis of xenografted tumors in athymic mice. These data suggest that CLDN1 promotes invasion and metastasis in cervical cancer cells via the expression of EMT/invasion-related genes. Therefore, CLDN1 could be a potential therapeutic target for the treatment of cervical cancer.
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