Abstract | BACKGROUND: METHODS: The CXCR4 expression, overall survival, and the clinical characteristics including age, sex, differentiation degree, tumor size, vascular invasion, lymph node metastasis, TNM stage, and T stage were analyzed for 122 IHCC patients. Short hairpin RNA ( shRNA) against CXCR4 was used to disrupt the CXCL12/CXCR4 signal transduction pathways in IHCC cell lines. In vitro assays, including CCK-8 assay, flow cytometry, and colony formation assay, and in vivo tumor formation assay were utilized to detect the cell phenotype of CXCR4 knockdown cells. Transwell and wound healing assays were used to examine the IHCC cell invasion and migration ability. The Wnt pathway was assessed by Western blot and β- Catenin/Tcf transcription reporter assay. RESULTS: We demonstrated that CXCR4 expression was closely correlated with IHCC progression and metastasis characteristics. The overall survival of patients with high CXCR4 expression was significantly lower than that of patients with low CXCR4 expression. Furthermore, we showed that the abrogation of CXCR4 had significantly negative influence on the IHCC cell phenotype, including in vitro cell proliferation, cell cycle, colony formation, cell invasion, and in vivo tumorigenicity. In addition, CXCR4 knockdown downregulated Wnt target genes and mesenchymal markers such as Vimentin and Slug. CONCLUSIONS: In conclusion, our result shows that high CXCR4 expression is associated with IHCC progression and metastasis via the canonical Wnt pathway, suggesting that CXCR4 may serve as a promising therapeutic target for IHCC.
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Authors | Shengqiang Zhao, Jing Wang, Chengyong Qin |
Journal | Journal of experimental & clinical cancer research : CR
(J Exp Clin Cancer Res)
Vol. 33
Pg. 103
(Dec 04 2014)
ISSN: 1756-9966 [Electronic] England |
PMID | 25471741
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- CXCL12 protein, human
- CXCR4 protein, human
- Chemokine CXCL12
- Receptors, CXCR4
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Topics |
- Animals
- Bile Duct Neoplasms
(genetics, metabolism, mortality, pathology, therapy)
- Biomarkers, Tumor
(genetics, metabolism)
- Cell Cycle
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Chemokine CXCL12
(metabolism)
- Cholangiocarcinoma
(genetics, metabolism, mortality, secondary, therapy)
- Disease Progression
- Female
- Humans
- Kaplan-Meier Estimate
- Male
- Mice, Nude
- Middle Aged
- Neoplasm Invasiveness
- RNA Interference
- RNAi Therapeutics
- Receptors, CXCR4
(genetics, metabolism)
- Time Factors
- Transfection
- Wnt Signaling Pathway
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