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.