Claudin-7 downregulation induces metastasis and invasion in colorectal cancer via the promotion of epithelial-mesenchymal transition.
Biochem Biophys Res Commun
; 508(3): 797-804, 2019 01 15.
Article
in En
| MEDLINE
| ID: mdl-30528239
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 HCT116â¯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 (râ¯=â¯0.725, pâ¯<â¯0.001) and upregulation of vimentin (râ¯=â¯-0.376, pâ¯=â¯0.001) and snail-1 (râ¯=â¯-0.599, pâ¯<â¯0.001). Additionally, in the claudin-7 knockdown HCT116â¯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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Claudins
/
Epithelial-Mesenchymal Transition
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2019
Type:
Article
Affiliation country:
China