Table 3 Characteristics of proteins associated with the cell surface expressed nucleolin.

Wnt related protein A and B. Protein A shares homology with human Wnt-7b [87], while protein B shares homology with Wnt-1 of the Mexican axolotl Ambystoma mexicanum [88]. The Wnt proteins are a family of secretory glycoproteins mostly associated with cell membranes and the extracellular matrix. They are implicated in proliferation and differentiation of both normal and malignant cells. Many members of the WNT gene family, including WNT-7, are up-regulated in bladder and breast carcinoma and as well as in chronic lymphocytic leukemia, suggesting involvement of Wnt signaling pathways in tumorigenesis [92–94].

80-kDa subunit of Ku. The Ku autoantigen is a heterodimeric protein made up of 70- and 80-kDa subunits. Besides its central importance to DNA repair, Ku has a key role in a number of other fundamental cellular processes such as telomere maintenance, transcription and cell death [89]. The cell surface expressed Ku80 is detected in a variety of tumor cells, including leukemia and solid tumor cells [95]. Surface Ku contributes to adhesion and invasion of tumor cells thus potentiating tumor metastasis [59].

SRP68 and SRP72. These are the 68- and 72-kDa subunit in the signal recognition particle, a ribonucleoprotein complex composed of 7S RNA and 6 proteins of 9-, 14-, 19-, 54-, 68-, 72-kDa. SRP comprise the major cellular machinery that mediates the cotranslational targeting of proteins to cellular membranes [60, 61]. SRP68 and SRP72 are functionally linked. Experimental evidence has demonstrated that SRP68 binds SRP72 and forms a highly stable heterodimer [96].

32-kDa protein referred to as p32/p33, HABP1, or gC1q-R. A multifunctional and muticompartmental cellular protein that was originally isolated based on its copurifiation with the nuclear splicing factor SF2 (p32/p33). It has also been described on the cell surface as the hyaluronan binding protein 1 (HABP1) and the receptor for complement component C1q (gC1q-R) [97]. Hyaluronan is a glycosaminoglycan that with its surface receptors regulate tumor cell adhesion, migration and invasion [98]. Preferentially over expressed in adenocarcinoma cells, gC1q-R is a molecular target in tumor cells and tumor stroma [90, 99]. In addition to cancer, gC1q-R is considered to play an important role in bacterial infections and inflammation [54, 55].

Ribosomal proteins S4 and S6. S4 and S6 are respectively components of the 40S and 60S ribosomal subunits, which generate ribosomal 80S subunit implicated in the cellular process of translation. Ribosomal proteins with nucleolin are also implicated in the processing and assembly of pre-ribosomal particles in the nucleolus. Like HB-19, several ribosomal proteins bind nucleolin via its RGG domain [9, 91]. The role, if any, of the surface expressed S4 and S6 remains to be investigated. It is worthwhile to note that several ribosomal protein genes have been reported to act as cancer genes in zebrafish [100].