PA 将肿瘤转移抑制蛋白 NDPK-A/NME1 递送至乳腺癌细胞中。
PA Delivers the Tumor Metastasis Suppressor Protein NDPK-A/NME1 into Breast Cancer Cells.
机构信息
Institute of Pharmacology and Toxicology, University Ulm Medical Center, 89081 Ulm, Germany.
Experimental Pharmacology, European Center for Angioscience, Mannheim Medical Faculty, Heidelberg University, 68167 Mannheim, Germany.
出版信息
Int J Mol Sci. 2020 May 6;21(9):3295. doi: 10.3390/ijms21093295.
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 protein toxins' transport component PA 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-tagged NDPK-A was detected in MDA-MB-231 cells via Western blotting and immunofluorescence microscopy. The PA-mediated delivery of His-NDPK-A resulted in reduced migration of MDA-MB-231 cells, as determined by a wound-healing assay. In conclusion, PA 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.
一些高转移性的乳腺癌类型表现出肿瘤抑制蛋白 NME1(也称为 nm23-H1 或核苷二磷酸激酶 A[NDPK-A])的细胞内水平降低,这会降低癌细胞的迁移和转移能力。由于其活性与患者的总体预后直接相关,因此增加此类癌细胞中 NDPK-A/NME1 的细胞质水平应该是减少肿瘤细胞迁移和降低转移的新治疗方法的一个有吸引力的起点。在这里,我们建立了蛋白毒素的转运成分 PA 作为将 His 标记的人 NDPK-A 递送至包括人 MDA-MB-231 乳腺癌细胞在内的培养细胞的细胞质中的转运体。通过 Western blot 和免疫荧光显微镜检测到在 MDA-MB-231 细胞中特异性递送至 His 标记的 NDPK-A。通过划痕愈合测定,PA 介导的 His-NDPK-A 递送至 MDA-MB-231 细胞中导致迁移活性降低。总之,PA 可将肿瘤转移抑制因子 NDPK-A/NME1 转运到体外人乳腺癌细胞的细胞质中,从而降低这些细胞的迁移活性。这种方法可能会导致新的治疗选择的发展。