<i>Bacillus anthracis’</i> PA<sub>63</sub> Delivers the Tumor Metastasis Suppressor Protein NDPK-A/NME1 into Breast Cancer Cells
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 o...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/9/3295 |
| _version_ | 1797568667892842496 |
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| author | Ina Felix Santosh K. Lomada Holger Barth Thomas Wieland |
| author_facet | Ina Felix Santosh K. Lomada Holger Barth Thomas Wieland |
| author_sort | Ina Felix |
| collection | DOAJ |
| description | 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 <i>Bacillus anthracis</i> protein toxins’ transport component PA<sub>63</sub> 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 His<sub>6</sub>-tagged NDPK-A was detected in MDA-MB-231 cells via Western blotting and immunofluorescence microscopy. The PA<sub>63</sub>-mediated delivery of His<sub>6</sub>-NDPK-A resulted in reduced migration of MDA-MB-231 cells, as determined by a wound-healing assay. In conclusion, PA<sub>63</sub> 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. |
| first_indexed | 2024-03-10T20:00:09Z |
| format | Article |
| id | doaj.art-3eb6c8446cee47ad9798bcea8196c717 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:00:09Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3eb6c8446cee47ad9798bcea8196c7172023-11-19T23:37:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-01219329510.3390/ijms21093295<i>Bacillus anthracis’</i> PA<sub>63</sub> Delivers the Tumor Metastasis Suppressor Protein NDPK-A/NME1 into Breast Cancer CellsIna Felix0Santosh K. Lomada1Holger Barth2Thomas Wieland3Institute of Pharmacology and Toxicology, University Ulm Medical Center, 89081 Ulm, GermanyExperimental Pharmacology, European Center for Angioscience, Mannheim Medical Faculty, Heidelberg University, 68167 Mannheim, GermanyInstitute of Pharmacology and Toxicology, University Ulm Medical Center, 89081 Ulm, GermanyExperimental Pharmacology, European Center for Angioscience, Mannheim Medical Faculty, Heidelberg University, 68167 Mannheim, GermanySome 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 <i>Bacillus anthracis</i> protein toxins’ transport component PA<sub>63</sub> 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 His<sub>6</sub>-tagged NDPK-A was detected in MDA-MB-231 cells via Western blotting and immunofluorescence microscopy. The PA<sub>63</sub>-mediated delivery of His<sub>6</sub>-NDPK-A resulted in reduced migration of MDA-MB-231 cells, as determined by a wound-healing assay. In conclusion, PA<sub>63</sub> 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.https://www.mdpi.com/1422-0067/21/9/3295tumor metastasis suppressor proteinNDPK-ANME1Nm23-H1anthrax toxinprotein transport |
| spellingShingle | Ina Felix Santosh K. Lomada Holger Barth Thomas Wieland <i>Bacillus anthracis’</i> PA<sub>63</sub> Delivers the Tumor Metastasis Suppressor Protein NDPK-A/NME1 into Breast Cancer Cells International Journal of Molecular Sciences tumor metastasis suppressor protein NDPK-A NME1 Nm23-H1 anthrax toxin protein transport |
| title | <i>Bacillus anthracis’</i> PA<sub>63</sub> Delivers the Tumor Metastasis Suppressor Protein NDPK-A/NME1 into Breast Cancer Cells |
| title_full | <i>Bacillus anthracis’</i> PA<sub>63</sub> Delivers the Tumor Metastasis Suppressor Protein NDPK-A/NME1 into Breast Cancer Cells |
| title_fullStr | <i>Bacillus anthracis’</i> PA<sub>63</sub> Delivers the Tumor Metastasis Suppressor Protein NDPK-A/NME1 into Breast Cancer Cells |
| title_full_unstemmed | <i>Bacillus anthracis’</i> PA<sub>63</sub> Delivers the Tumor Metastasis Suppressor Protein NDPK-A/NME1 into Breast Cancer Cells |
| title_short | <i>Bacillus anthracis’</i> PA<sub>63</sub> Delivers the Tumor Metastasis Suppressor Protein NDPK-A/NME1 into Breast Cancer Cells |
| title_sort | i bacillus anthracis i pa sub 63 sub delivers the tumor metastasis suppressor protein ndpk a nme1 into breast cancer cells |
| topic | tumor metastasis suppressor protein NDPK-A NME1 Nm23-H1 anthrax toxin protein transport |
| url | https://www.mdpi.com/1422-0067/21/9/3295 |
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