Possible Mechanisms for Regulation of Breast Tumor Micrometastasis by NME Genes

摘要

Metastatic dissemination of primary breast tumors is controlled by positive andnegative regulators. We found that expression of a catalytically inactive nucleoside diphosphate kinase B (NDPK B/T) in MDA-MB-435 human breast carcinoma cells significantly decreases their metastatic dissemination in a nude mouse assay. Inhibition of metastatic dissemination of primary tumors formed by these cells occurs prior to formation of detectable micrometastasis. Our structural studies suggests that wild type NDPK B and highly homologous NDPK A form different oligomers that may occupy specific binding sites We hypothesize that NDPK B/T displaces wild type NDPK B from specific binding sites, acting in effect as a dominant negative mutant. These results suggest that NDPK B acts as a positive regulator of metastatic potential of human tumor cells and that specific inhibition of NDPK B may be a target for potential anti-metastasis therapeutics.