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Slug signaling is up-regulated by CCL21/CXCR7 to induce EMT in human chondrosarcoma

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An Erratum to this article was published on 06 February 2015

Abstract

In recent decades, the CXC chemokine receptor 7 (CXCR7) and its ligand CCL21 have been extensively reported to be associated with tumorigenesis. Meanwhile, Slug signaling induces the epithelial-mesenchymal transition (EMT) process in chondrosarcoma development. In the present study, we explored the functions of CCL21/CXCR7 in Slug-mediated EMT in the chondrosarcoma. We analyzed protein expression of CXCR7 and Slug in human chondrosarcoma samples. Effects of CXCR7 on chondrosarcoma cells were assessed by in vitro assays. Additionally, CXCR7 pathways were further investigated by pharmacological and genetic approaches. We found that the altered CXCR7 (81.7 %) and Slug (85.0 %) expression in human chondrosarcoma tissues were significantly associated with grade, recurrence, and 5-year overall survival. According to in vitro assays, CCL21 stimulation induced the expression of phosph-ERK, phosph-AKT, Slug and N-cadherin in SW1353 cells, while the expression of E-cadherin was down-regulated. Furthermore, Slug signaling modulated E- to N-cadherin switch, which was influenced by the kinase inhibitor PD98059 and LY294002. In addition, the genetic silencing of Slug inhibited the capacity of migration and invasion of SW1353 cells. In conclusion, CCL21/CXCR7 pathway activates ERK and PI3K/AKT signallings to up-regulate Slug pathway, leading to the occurrence of EMT process in human chondrosarcoma. This study lays a new foundation for molecule-targeted therapy of human chondrosarcoma.

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Acknowledgments

We gratefully thank Mingtang He and Ziqing Zhang for their critical reading of this paper and valuable suggestions.

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Authors and Affiliations

  1. Department of Orthopedics, Longgang Orthopedics Hospital of Shenzhen, 243# Yangmeigang, Longgang Street, Longgang District, Shenzhen, 518116, Guangdong, China

    Guosong Li, Yanjun Yang, Siliang Xu, Lifeng Ma, Mingtang He & Ziqing Zhang

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  1. Guosong Li
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  2. Yanjun Yang
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  3. Siliang Xu
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  4. Lifeng Ma
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  5. Mingtang He
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Correspondence to Ziqing Zhang.

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Li, G., Yang, Y., Xu, S. et al. Slug signaling is up-regulated by CCL21/CXCR7 to induce EMT in human chondrosarcoma. Med Oncol 32, 2 (2015). https://doi.org/10.1007/s12032-014-0478-6

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  • DOI: https://doi.org/10.1007/s12032-014-0478-6

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