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Open AccessArticle

Bacillus anthracis’ PA63 Delivers the Tumor Metastasis Suppressor Protein NDPK-A/NME1 into Breast Cancer Cells

by Ina Felix 1, Santosh K. Lomada 2,3, Holger Barth 1,*,† and Thomas Wieland 2,3,*,†
1
Institute of Pharmacology and Toxicology, University Ulm Medical Center, 89081 Ulm, Germany
2
Experimental Pharmacology, European Center for Angioscience, Mannheim Medical Faculty, Heidelberg University, 68167 Mannheim, Germany
3
DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Germany
*
Authors to whom correspondence should be addressed.
The corresponding authors share the senior authorship.
Int. J. Mol. Sci. 2020, 21(9), 3295; https://doi.org/10.3390/ijms21093295
Received: 21 April 2020 / Revised: 30 April 2020 / Accepted: 4 May 2020 / Published: 6 May 2020
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. View Full-Text
Keywords: tumor metastasis suppressor protein; NDPK-A; NME1; Nm23-H1; anthrax toxin; protein transport; targeted drug delivery; protective antigen PA63 tumor metastasis suppressor protein; NDPK-A; NME1; Nm23-H1; anthrax toxin; protein transport; targeted drug delivery; protective antigen PA63
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Felix, I.; Lomada, S.K.; Barth, H.; Wieland, T. Bacillus anthracis’ PA63 Delivers the Tumor Metastasis Suppressor Protein NDPK-A/NME1 into Breast Cancer Cells. Int. J. Mol. Sci. 2020, 21, 3295.

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