CLDN1 expression in cervical cancer cells is related to tumor invasion and metastasis.
CLDN1 expression in cervical cancer cells is related to tumor invasion and metastasis.
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宫颈癌细胞中CLDN1表达与肿瘤侵袭转移相关
DOI：
10.18632/oncotarget.13871
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发表时间：
2016-12-27
期刊：
影响因子：
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通讯作者：
Wang H
中科院分区：
文献类型：
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作者：
Zhang WN;Li W;Wang XL;Hu Z;Zhu D;Ding WC;Liu D;Li KZ;Ma D;Wang H
尽管人乳头瘤病毒（HPV）感染非常重要，但它并非宫颈癌的唯一病因。因为已知由HPV感染导致的基因变异可能是宫颈癌最重要的病因，所以我们采用人类全基因组阵列比较基因组杂交技术来检测宫颈鳞状细胞癌中基因的拷贝数变异。阵列结果通过聚合酶链反应（PCR）、荧光原位杂交（FISH）和免疫组织化学进行了验证。我们发现紧密连接蛋白 -1（CLDN1）的拷贝数和蛋白表达随着宫颈癌的进展而增加。宫颈淋巴结转移组中CLDN1的强阳性染色评分显著高于宫颈癌组织无淋巴结转移组的染色评分。SiHa细胞中CLDN1的过表达可增强抗凋亡能力并促进这些细胞的侵袭能力，同时上皮标志物E - 钙黏蛋白表达降低，间质标志物波形蛋白表达增加。CLDN1通过与SNAI1相互作用诱导上皮 - 间质转化（EMT）。此外，我们证明CLDN1过表达对无胸腺小鼠移植瘤的生长和转移有显著影响。这些数据表明CLDN1通过EMT/侵袭相关基因的表达促进宫颈癌细胞的侵袭和转移。因此，CLDN1可能是治疗宫颈癌的一个潜在治疗靶点。
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.