Nm23 belongs to the family of nucleoside diphosphate kinases (NDPKs) and ten isoforms (Nm23-H1 to -H10) have been identified in human, of which Nm23-H1 and -H2 attract most interest. Nm23-H1 is generally regarded as a prototypical metastasis suppressor. In the present study, both Nm23-H1 and -H2 can suppress cell migration and one mechanism behind this may be through regulation of E-cadherin and vimentin. Although early studies examining the metastasis suppressive function of Nm23 did not reveal any significant effect on tumorigenesis, recent studies suggest that Nm23-H1 can inhibit the function of Ras GTPases and facilitate the p53 signaling pathway. As dysregulation of Ras or/and p53 are commonly found in human cancers, the involvement of Nm23-H1 in the two pathways suggests...[ Read more ]

Nm23 belongs to the family of nucleoside diphosphate kinases (NDPKs) and ten isoforms (Nm23-H1 to -H10) have been identified in human, of which Nm23-H1 and -H2 attract most interest. Nm23-H1 is generally regarded as a prototypical metastasis suppressor. In the present study, both Nm23-H1 and -H2 can suppress cell migration and one mechanism behind this may be through regulation of E-cadherin and vimentin. Although early studies examining the metastasis suppressive function of Nm23 did not reveal any significant effect on tumorigenesis, recent studies suggest that Nm23-H1 can inhibit the function of Ras GTPases and facilitate the p53 signaling pathway. As dysregulation of Ras or/and p53 are commonly found in human cancers, the involvement of Nm23-H1 in the two pathways suggests the possible regulatory functions of Nm23 on tumorigenesis. Here, I employed both cellular and in vivo assays to examine the effect of Nm23-H1 and -H2 on tumorigenesis induced by oncogenic Ras or/and p53 deficiency. Co-expression of Nm23-H1 but not -H2 in NIH3T3 cells effectively suppressed neoplastic transformation and tumorigenesis induced by the oncogenic H-Ras G12V (Ras^GV) mutant. Overexpression of Nm23-H1 but not -H2 also inhibited tumorigenesis by human cervical cancer HeLa cells that represent a well-studied model for p53 deficiency. However, in human non-small-cell lung carcinoma H1299 cells harboring N-Ras Q61K oncogenic mutation and p53 deletion, overexpression of Nm23-H1 did not affect tumorigenesis. Interestingly, overexpression of Nm23-H2 facilitated tumorigenesis of H1299 cells. Previous studies found that the conditioned media from serum-deprived RGS19/293 cells supported the growth of HEK293 in the absence of serum and Nm23 protein was detected in the conditioned media. So it would be interesting to investigate whether exogenously added Nm23 protein can support cell growth. However, this study indicates extracellular Nm23 protein alone, is not sufficient to stimulate cell growth. Collectively, these results suggest that Nm23-H1 and -H2 have similar functions to suppress cell migration but have differential abilities to modulate tumorigenesis dependent on cell context, and that extracellular Nm23 protein alone cannot support cell growth.