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Glycochenodeoxycholate promotes the metastasis of gallbladder cancer cells by inducing epithelial to mesenchymal transition via activation of SOCS3/JAK2/STAT3 signaling pathway
Author(s) -
Wang Hui,
Zhan Ming,
Liu Qiang,
Wang Jian
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29080
Subject(s) - epithelial–mesenchymal transition , socs3 , metastasis , cancer research , stat3 , cancer , signal transduction , mesenchymal stem cell , chemistry , medicine , biology , microbiology and biotechnology
The incidence of gallbladder cancer (GBC) is relatively rare but a high degree of malignancy. The migration and invasion potential of GBC severely affects the prognosis of patients with GBC. Glycochenodeoxycholate (GCDC) is one of the most important components in GBC‐associated microenvironment. However, the role of GCDC in the metastatic feature of GBC cells is not fully understood. First, the results of this study found that GCDC could effectively enhance the metastasis of GBC cells. Furthermore, GCDC could lead to the enhancement of epithelial to mesenchymal transition (EMT) phenotype in GBC cells, which is concerned to be an important mechanism of tumor metastasis. Further studies showed that GCDC treatment induced the upregulation of matrix metalloproteinase‐3 (MMP3), MMP9, and SOCS3/JAK2/p‐STAT3 signal pathway in GBC cells, which could regulate the level of EMT. Beside that, we also found the positive expression of farnesoid X receptor (FXR) in GBC cells and inhibition of FXR could significantly block the effect of GCDC on the metastasis of GBC cells. These results indicated that GCDC promoted GBC cells metastasis by enhancing the level of EMT and inhibition of FXR could significantly block the effect of GCDC. On one hand, FXR might be an indicator for predicting the metastasis of patient with GBC. On the other hand, FXR might serve as a potential antimetastasis target in GBC therapy.