1. Mitochondrial NME6 Influences Basic Cellular Processes in Tumor Cells In Vitro.
- Author
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Proust B, Horvat A, Tadijan A, Vlašić I, and Herak Bosnar M
- Subjects
- Humans, Cell Line, Tumor, Breast Neoplasms genetics, Breast Neoplasms metabolism, Breast Neoplasms pathology, Apoptosis genetics, Nucleoside Diphosphate Kinase D metabolism, Nucleoside Diphosphate Kinase D genetics, Female, Gene Expression Regulation, Neoplastic, MAP Kinase Signaling System, Cell Cycle genetics, Mitochondria metabolism, Mitochondria genetics, Cell Movement genetics, Epithelial-Mesenchymal Transition genetics
- Abstract
NME6 belongs to the family of nucleoside diphosphate kinase enzymes, whose major role is to transfer the terminal phosphate from NTPs, mostly ATP, to other (d)NDPs via a high-energy intermediate. Beside this basic enzymatic activity, the family, comprising 10 genes/proteins in humans, executes a number of diverse biochemical/biological functions in the cell. A few previous studies have reported that NME6 resides in the mitochondria and influences oxidative phosphorylation while interacting with RCC1L, a GTPase involved in mitochondrial ribosome assembly and translation. Considering the multifunctional role of NME family members, the goal of the present study was to assess the influence of the overexpression or silencing of NME6 on fundamental cellular events of MDA-MB-231T metastatic breast cancer cells. Using flow cytometry, Western blotting, and a wound-healing assay, we demonstrated that the overexpression of NME6 reduces cell migration and alters the expression of EMT (epithelial-mesenchymal transition) markers. In addition, NME6 overexpression influences cell cycle distribution exclusively upon DNA damage and impacts the MAPK/ERK signaling pathway, while it has no effect on apoptosis. To conclude, our results demonstrate that NME6 is involved in different cellular processes, providing a solid basis for future, more precise investigations of its role.
- Published
- 2024
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