Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China; Cancer Hospital Chinese Academy of Medical Sciences, Peking Union Medical College, 100021, China.
Biochem Biophys Res Commun. 2019 Jan 15;508(3):797-804. doi: 10.1016/j.bbrc.2018.10.049. Epub 2018 Dec 6.
The dysregulation of the tight junctions (TJs) protein claudin-7 is closely related to the development and metastasis of colorectal cancer (CRC). The aim of this study was to investigate the expression of claudin-7 and characterize the relationship between claudin-7 expression and epithelial-mesenchymal transition (EMT) in CRC. In this study, the expression of claudin-7, E-cadherin, vimentin and snail-1 was detected by immunohistochemistry (IHC) in a set of 80 CRC specimens comprising 20 specimens each of well-differentiated, moderately differentiated, poorly differentiated and liver metastases tissues. The correlation between claudin-7 and EMT-related proteins in the stably transfected claudin-7 knockdown HCT116 cell line was analyzed by IHC, immunofluorescence (IF), Western blotting (WB) and nude mouse xenograft models. The results revealed that the expression of claudin-7 was downregulated as CRC tissue differentiation grade decreased, and that low claudin-7 expression corresponded to the downregulation of E-cadherin (r = 0.725, p < 0.001) and upregulation of vimentin (r = -0.376, p = 0.001) and snail-1 (r = -0.599, p < 0.001). Additionally, in the claudin-7 knockdown HCT116 cell line, the staining intensity and expression of E-cadherin was decreased, while the immunoreactivity and expression of vimentin and snail-1 was increased. Futhermore, the result of tumor formation experiment was consistent with CRC tissues. In conclusion, the expression of claudin-7 in CRC is downregulated as differentiation grade decreases. Claudin-7 downregulation may promote the invasion and metastasis of CRC by regulating EMT. Our results provide new perspectives for a potential therapeutic target for CRC.
紧密连接（TJs）蛋白 Claudin-7 的失调与结直肠癌（CRC）的发生和转移密切相关。本研究旨在探讨 Claudin-7 的表达，并研究其与 CRC 上皮间质转化（EMT）之间的关系。本研究采用免疫组织化学（IHC）方法检测 80 例 CRC 标本中 Claudin-7、E-钙黏蛋白、波形蛋白和 SNAIL1 的表达，包括 20 例分化良好、中等分化、低分化和肝转移组织的标本。通过 IHC、免疫荧光（IF）、Western blot（WB）和裸鼠异种移植模型分析稳定转染 Claudin-7 敲低的 HCT116 细胞系中 Claudin-7 与 EMT 相关蛋白的相关性。结果显示，随着 CRC 组织分化程度的降低，Claudin-7 的表达下调，Claudin-7 低表达与 E-钙黏蛋白下调（r=0.725，p<0.001）、波形蛋白上调（r=-0.376，p=0.001）和 SNAIL1 上调（r=-0.599，p<0.001）相关。此外，在 Claudin-7 敲低的 HCT116 细胞系中，E-钙黏蛋白的染色强度和表达降低，而波形蛋白和 SNAIL1 的免疫反应性和表达增加。此外，肿瘤形成实验的结果与 CRC 组织一致。综上所述，CRC 中 Claudin-7 的表达随分化程度的降低而下调。Claudin-7 的下调可能通过调节 EMT 促进 CRC 的侵袭和转移。我们的研究结果为 CRC 的潜在治疗靶点提供了新的视角。
