Tumor Biology

, Volume 35, Issue 1, pp 333–338 | Cite as

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

  • Xiangshan Yang
  • Zhongfa Xu
  • Daotang Li
  • Shaomei Cheng
  • Kaixi Fan
  • Chengjun Li
  • Aiping Li
  • Jing Zhang
  • Man Feng
Research Article


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.


Cell surface nucleolin CXCR4 Interaction Papillary thyroid carcinoma 



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

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Xiangshan Yang
    • 1
  • Zhongfa Xu
    • 2
  • Daotang Li
    • 3
  • Shaomei Cheng
    • 4
  • Kaixi Fan
    • 5
  • Chengjun Li
    • 2
  • Aiping Li
    • 6
  • Jing Zhang
    • 1
  • Man Feng
    • 1
  1. 1.Department of PathologyAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina
  2. 2.Department of General SurgeryAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina
  3. 3.Department of Thoracic SurgeryAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina
  4. 4.Department of GynecologyAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina
  5. 5.Center LaboratoryAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina
  6. 6.Department of MedicineAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina

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