SDF-1/CXCR4 promotes epithelial–mesenchymal transition and progression of colorectal cancer by activation of the Wnt/β-catenin signaling pathway
Copyright policy )SDF-1/CXCR4 promotes epithelial–mesenchymal transition and progression of colorectal cancer by activation of the Wnt/β-catenin signaling pathway
Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in angiogenesis and are associated with tumor progression. This study aimed to investigate the role of SDF-1/CXCR4-mediated epithelial-mesenchymal transition (EMT) and the progression of colorectal cancer (CRC) as well as the underlying mechanisms. The data showed that expression of CXCR4 and β-catenin mRNA and protein was significantly higher in CRC tissues than in distant normal tissues. CXCR4 expression was associated with β-catenin expression in CRC tissues, whereas high CXCR4 expression was strongly associated with low E-cadherin, high N-cadherin, and high vimentin expression, suggesting a cross talk between the SDF-1/CXCR4 axis and Wnt/β-catenin signaling pathway in CRC. In vitro, SDF-1 induced CXCR4-positive colorectal cancer cell invasion and EMT by activation of the Wnt/β-catenin signaling pathway. In contrast, SDF-1/CXCR4 axis activation-induced colorectal cancer invasion and EMT was effectively inhibited by the Wnt signaling pathway inhibitor Dickkopf-1. In conclusion, CXCR4-promoted CRC progression and EMT were regulated by the Wnt/β-catenin signaling pathway. Thus, targeting of the SDF-1/CXCR4 axis could have clinical applications in suppressing CRC progression.
- Xi’an Jiaotong-Liverpool University China (People's Republic of)
Male, Receptors, CXCR4, Epithelial-Mesenchymal Transition, Mice, Nude, Middle Aged, Chemokine CXCL12, Mice, Gene Knockdown Techniques, Disease Progression, Animals, Heterografts, Humans, Intercellular Signaling Peptides and Proteins, Female, Colorectal Neoplasms, Wnt Signaling Pathway, beta Catenin
Male, Receptors, CXCR4, Epithelial-Mesenchymal Transition, Mice, Nude, Middle Aged, Chemokine CXCL12, Mice, Gene Knockdown Techniques, Disease Progression, Animals, Heterografts, Humans, Intercellular Signaling Peptides and Proteins, Female, Colorectal Neoplasms, Wnt Signaling Pathway, beta Catenin
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