Nodal induces epithelial-mesenchymal transition in gallbladder carcinoma via the Smad2/4 pathway
10.3760/cma.j.issn.1007-8118.2018.09.005
- VernacularTitle:胆囊癌细胞Nodal表达对Smad2/4信号通路及上皮间质转化的影响
- Author:
Yang WANG
1
;
Yingbin HUANG
;
Guangyu CHEN
;
Rui HE
;
Jun DU
;
Canqiao LUO
;
Xingyuan JIAO
Author Information
1. 510080,中山大学附属第一医院肝胆病诊疗中心
- Keywords:
Gallbladder carcinoma,Gallstone;
Transforming growth factor-beta,Nodal;
Smad2/4,signal conduction;
Epithelial-mesenchymal transition
- From:
Chinese Journal of Hepatobiliary Surgery
2018;24(9):594-599
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the expressions of Nodal in normal gallbladder,and gallbladders with cholelithiasis,cholecystitis and carcinoma;and to study the impact of inhibiting or promoting Nodal expressions in gallbladder carcinoma on the Smad2/4 pathway and epithelial-mesenchymal transition.Methods Immunohistochemistry was used to detect the expressions and distributions of Nodal protein in 30 normal gallbladders,96 simple cholecystitis/calculous cholecystitis specimens and 42 gallbladder carcinoma specimens.The mRNA and protein expressions of Nodal in normal and malignant gallbladdcr mucosal epithelium cells and breast cancer cells were detected by RT-PCR,western blotting and wound healing tests.The impact of activating agents and inhibitors on the expression levels of Nodal and its signaling pathway Smad2/4 and EMT-related proteins were analyzed.Results Immunohistochemistry showed that the positive rates of Nodal in the gallbladder cancer group was significantly higher than that in the gallbladder stone group and the normal gallbladder group.The results were 83.3％ (35/42),44.8％ (43/96),6.7％ (2/30) respectively (P＜ 0.01).RT-PCR and Western blotting showed the expressions of Nodal in gallbladder carcinoma cells were higher than normal gallbladder cells (P＜0.05).After using rhNodal to up regulate the Nodal expression,the Smad2 protein phosphorylation was promoted and the EMT associated proteins were up-regulated.After using the inhibitor SB431542 to suppress the Nodal expression,the Smad2 protein phosphorylation decreased and the EMT associated proteins were down-regulated.Conclusions The expression of Nodal was closely related to cell proliferation and metastasis in gallbladder carcinoma.Tumor progression was promoted via the smad2/4 pathway through epithelial-mesenchymal transition.
