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Cell surface nucleolin is crucial in the activation of the CXCL12/CXCR4 signaling pathway

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Tumor Biology

Abstract

Recently, CXCL12–CXCR4 has been focused on therapeutic strategies for papillary thyroid carcinoma (PTC) and other cancers. At the same time, cell surface nucleolin is also over-expressed in PTC and others. Interestingly, a few reports suggest that either CXCR4 or cell surface nucleolin is a co-receptor for HIV-1 entry into CD4+ T cells, which indicates that there is a relationship between CXCR4 and nucleolin. In this study, antibody and siRNA were used to identify effects of cell surface nucleolin and CXCR4 on cell signaling; soft-agar colony formation assay and Transwell assay were used to determine roles of nucleolin and CXCR4 in cell proliferation and migration. Importantly, co-immunoprecipitation was used to demonstrate the relationship between CXCR4 and nucleolin. Results showed CXCR4 and nucleolin were co-expressed in PTC cell line K1, B-CPAP, and TPC-1. Either cell surface nucleolin or CXCR4 was necessary to prompt extracellular signal-regulated kinase phosphorylation. When blocked, CXCR4 or nucleolin can significantly affect TPC-1 proliferation and migration (p < 0.01). Co-immunoprecipitation analysis identified that nucleolin can bind and interact with CXCR4 to activate CXCR4 signaling. This study suggests that nucleolin is crucial in the activation of CXCR4 signaling, which affects cell growth, migration, and invasiveness. Further, nucleolin may interact with other receptors. Our study also offers new ideas for cancer therapy.

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Acknowledgments

We gratefully acknowledge other members of the Yang Group for their critical reading of this paper and valuable suggestions.

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Authors and Affiliations

  1. Department of Pathology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong, China

    Xiangshan Yang, Jing Zhang & Man Feng

  2. Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong, China

    Zhongfa Xu & Chengjun Li

  3. Department of Thoracic Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong, China

    Daotang Li

  4. Department of Gynecology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong, China

    Shaomei Cheng

  5. Center Laboratory, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong, China

    Kaixi Fan

  6. Department of Medicine, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong, China

    Aiping Li

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  1. Xiangshan Yang
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  2. Zhongfa Xu
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  8. Jing Zhang
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  9. Man Feng
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Correspondence to Xiangshan Yang.

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Yang, X., Xu, Z., Li, D. et al. Cell surface nucleolin is crucial in the activation of the CXCL12/CXCR4 signaling pathway. Tumor Biol. 35, 333–338 (2014). https://doi.org/10.1007/s13277-013-1044-0

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  • DOI: https://doi.org/10.1007/s13277-013-1044-0

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