Tumor Biology

, Volume 36, Issue 2, pp 1099–1104 | Cite as

Cell surface nucleolin interacts with CXCR4 receptor via the 212 c-terminal portion

  • Hongxin Niu
  • Xiangshan Yang
  • Zhongfa Xu
  • Tong Du
  • Ruogu Wang
Research Article


Previously, we reported that CXCR4 receptor interacted with cell surface nucleolin, and the synergy of CXCR4 and nucleolin plays an essential role in malignant transformation. Here, we continued to conduct a structure–function analysis of nucleolin to identify which portion can efficaciously bind to CXCR4. In the present study, the expression of CXCR4 and nucleolin in 100 cases of papillary thyroid cancer (PTC) samples was investigated through immunohistochemistry (IHC). Subsequently, using nucleolin mutants and pull-down assay, we investigated precise interactions between CXCR4 and nucleolin in HEK-293 cells. A previous study demonstrated CXCR4 and nucleolin co-expressed in cell lines, and the present study further identified that CXCR4 and nucleolin co-expressed in PTC tissues, instead of normal tissues. The nucleolin mutant analysis revealed that nucleolin can efficaciously bind CXCR4 to activate CXCR4 signaling by 212 c-terminal domain. Conversely, n-terminal, RBD and GAR mutants of nucleolin showed no sign of activation of CXCR4 signaling, and differences were statistically insignificant (p > 0.05). In conclusion, these results suggested nucleolin is essential to activate CXCR4 signaling via 212 c-terminal domain, which is required for cell growth, migration, and invasiveness. Furthermore, nucleolin may interact with more G protein-coupled receptors, at least chemokine receptor. Our study will lay a new foundation for cancer therapy by antagonizing nucleolin and CXCR4.


Nucleolin 212 c-terminal portion CXCR4 Activation 



We gratefully thank the other members of Yang Lab 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) 2014

Authors and Affiliations

  • Hongxin Niu
    • 1
  • Xiangshan Yang
    • 2
  • Zhongfa Xu
    • 1
  • Tong Du
    • 1
  • Ruogu Wang
    • 1
  1. 1.Department of General SurgeryAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina
  2. 2.Department of PathologyAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina

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