Claudin-7 downregulation induces metastasis and invasion in colorectal cancer via the promotion of epithelial-mesenchymal transition |
| |
Authors: | Kun Wang Tengyan Li Chang Xu Yuhan Ding Wenjing Li Lei Ding |
| |
Affiliation: | 1. Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China;2. Cancer Hospital Chinese Academy of Medical Sciences, Peking Union Medical College, 100021, China;3. Binzhou Medical University Hospital, Binzhou City, 256603, Shandong Province, China |
| |
Abstract: | 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. |
| |
Keywords: | Claudin-7 Epithelial-mesenchymal transition Colorectal cancer Metastasis TJs Tight junctions CRC Colorectal cancer EMT Epithelial-mesenchymal transition |
本文献已被 ScienceDirect 等数据库收录! |
|