Blockade of CXCL12/CXCR4 signaling inhibits intrahepatic cholangiocarcinoma progression and metastasis via inactivation of canonical Wnt pathway

摘要: Intrahepatic cholangiocarcinoma (IHCC) is the second most frequent primary malignant liver tumor following hepatocellular carcinoma. It a highly fatal disease and has few therapeutics. The CXC chemokine ligand-12 (CXCL12)/CXC receptor type 4 (CXCR4) axis been shown to be involved in tumorgenesis, proliferation, angiogenesis variety of cancers including IHCC. However, its prognostic significance IHCC unclear. purpose this study was examine functional role CXCR4 progression metastasis explore underlying mechanism. expression, overall survival, clinical characteristics age, sex, differentiation degree, size, vascular invasion, lymph node metastasis, TNM stage, T stage were analyzed for 122 patients. Short hairpin RNA (shRNA) against used disrupt CXCL12/CXCR4 signal transduction pathways cell lines. In vitro assays, CCK-8 assay, flow cytometry, colony formation vivo assay utilized detect phenotype knockdown cells. Transwell wound healing assays invasion migration ability. Wnt pathway assessed by Western blot β-Catenin/Tcf transcription reporter assay. We demonstrated that expression closely correlated with characteristics. survival patients high significantly lower than low expression. Furthermore, we showed abrogation had negative influence on phenotype, cycle, formation, tumorigenicity. addition, downregulated target genes mesenchymal markers such as Vimentin Slug. conclusion, our result shows associated via canonical pathway, suggesting may serve promising therapeutic