Claudin-3 Inhibits Lung Squamous Cell Carcinoma Cell Epithelial-mesenchymal Transition and Invasion via Suppression of the Wnt/β-catenin Signaling Pathway.
Claudin-3 Inhibits Lung Squamous Cell Carcinoma Cell Epithelial-mesenchymal Transition and Invasion via Suppression of the Wnt/β-catenin Signaling Pathway.
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Claudin-3 通过抑制 Wnt/β-catenin 信号通路抑制肺鳞状细胞癌细胞上皮间质转化和侵袭
DOI：
10.7150/ijms.22927
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发表时间：
2018
影响因子：
3.6
通讯作者：
Cao B
中科院分区：
文献类型：
--
作者：
Che J;Yue D;Zhang B;Zhang H;Huo Y;Gao L;Zhen H;Yang Y;Cao B
紧密连接蛋白3（claudin-3，CLDN 3）是上皮细胞紧密连接的关键细胞骨架结构蛋白，其表达改变与多种人类癌症的发展和转移相关。CLDN 3表达与肺鳞状细胞癌（SqCC）的预后显著相关。本研究探讨了CLDN 3在抑制肺SqCC细胞迁移和侵袭中的作用以及潜在的分子机制。使用定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹评估20对肺SqCC组织和相邻正常组织之间的CLDN 3水平。通过分别使用携带CLDN 3 cDNA或shRNA的质粒产生异位CLDN 3过表达或敲低。与邻近的正常组织相比，肺SqCC组织中CLDN 3表达显著降低。异位CLDN 3过表达显著抑制肺癌H520细胞的迁移、侵袭和上皮-间质转化（EMT），而CLDN 3敲低对SK-MES-1细胞具有相反的作用。然而，细胞活力和平板集落形成测定显示CLDN 3敲低和过表达均不影响SqCC细胞增殖。组织和细胞数据均显示，CLDN 3表达与EMT生物标志物E-钙粘蛋白和波形蛋白的表达显著相关。此外，CLDN 3调节EMT和EMT标志物的表达是通过调节Wnt/β-连环蛋白信号传导途径。总之，该研究鉴定了肺SqCC组织中CLDN 3表达的降低，其与肺SqCC的进展和转移相关，并且归因于通过Wnt途径的激活的EMT。因此，CLDN 3可作为一种新的生物标志物，用于预测肺SqCC的预后，并作为未来治疗肺SqCC的靶点。
Altered expression of claudin-3 (CLDN3), a key cytoskeletal structural protein of the tight junctions in the epithelium, is associated with the development and metastasis of various human cancers. CLDN3 expression has been shown to be significantly associated with the prognosis of lung squamous cell carcinoma (SqCC). This study investigated the role of CLDN3 in inhibiting lung SqCC cell migration and invasion as well as the underlying molecular mechanisms. The CLDN3 levels were assessed between 20 paired lung SqCC tissues and adjacent normal tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The ectopic CLDN3 overexpression or knockdown was generated by using a plasmid carrying CLDN3 cDNA or shRNA, respectively. CLDN3 expression was significantly reduced in lung SqCC tissues vs. the adjacent normal tissues. The ectopic CLDN3 overexpression markedly inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of lung cancer H520 cells, whereas CLDN3 knockdown had an inverse effect on SK-MES-1 cells. However, cell viability and plate colony formation assays showed that both CLDN3 knockdown and overexpression did not affect SqCC cell proliferation. Both tissue and cell data revealed that CLDN3 expression was significantly associated with the expression of the EMT biomarkers E-cadherin and Vimentin. Furthermore, CLDN3-modulated EMT and expression of the EMT markers were through regulation of the Wnt/β-catenin signaling pathway. In conclusion, this study identified reduced CLDN3 expression in lung SqCC tissues, which was associated with the progression and metastasis of lung SqCC and was attributed to EMT by activation of the Wnt pathway. Thus, CLDN3 could be further evaluated as a novel biomarker for predicting the prognosis of lung SqCC and as a target for the treatment of lung SqCC in the future.
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影响因子：
4.8
作者：
Shang, Xiying;Lin, Xinjian;Howell, Stephen B.
通讯作者：
Howell, Stephen B.
影响因子：
158.5
作者：
AUERBACH, O;HAMMOND, EC;GARFINKEL, L
通讯作者：
GARFINKEL, L
DOI：
10.1097/01.pai.0000151933.04800.1c
发表时间：
2006-03-01
影响因子：
1.6
作者：
Montgomery, E;Mamelak, AJ;Berg, KD
通讯作者：
Berg, KD
DOI：
10.1152/ajplung.00299.2010
发表时间：
2011-07-01
影响因子：
4.9
作者：
Mitchell, Leslie A.;Overgaard, Christian E.;Koval, Michael
通讯作者：
Koval, Michael
影响因子：
2.8
作者：
Moldvay, Judit;Fabian, Katalin;Schaff, Zsuzsa
通讯作者：
Schaff, Zsuzsa