Some highly metastatic types of
breast cancer show decreased intracellular levels of the
tumor suppressor protein NME1, also known as nm23-H1 or
nucleoside diphosphate kinase A (NDPK-A), which decreases
cancer cell motility and
metastasis. Since its activity is directly correlated with the overall outcome in patients, increasing the cytosolic levels of NDPK-A/NME1 in such
cancer cells should represent an attractive starting point for novel therapeutic approaches to reduce
tumor cell motility and decrease
metastasis. Here, we established the Bacillus anthracis
protein toxins' transport component PA63 as transporter for the delivery of His-tagged human NDPK-A into the cytosol of cultured cells including human MDA-MB-231
breast cancer cells. The specifically delivered His6-tagged NDPK-A was detected in MDA-MB-231 cells via Western blotting and immunofluorescence microscopy. The PA63-mediated delivery of His6-NDPK-A resulted in reduced migration of MDA-MB-231 cells, as determined by a wound-healing assay. In conclusion, PA63 serves for the transport of the
tumor metastasis suppressor NDPK-A/NME1 into the cytosol of human
breast cancer cells in vitro, which reduced the migratory activity of these cells. This approach might lead to development of novel therapeutic options.