Mitochondrial ferritin, a new target for inhibiting neuronal tumor cell proliferation
| Autor: | Bao Lu Zhao, Zhen Hua Shi, Fang Fang Shi, Chun Yan Li, Lin Hao You, Hong Meng Xu, Ya Shuo Zhao, Yue Qi Wang, Xiang Lin Duan, Guangjun Nie, Yan Zhong Chang, Alex D. Sheftel, Yu Jing Gou |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Mice Nude Apoptosis Cell Cycle Proteins Transferrin receptor Cell cycle Retinoblastoma Protein Cyclin-dependent protein kinase Proto-Oncogene Proteins c-myc Neuroblastoma Mice Cellular and Molecular Neuroscience Downregulation and upregulation Cell Line Tumor Cyclin E Animals Humans Cyclin D1 Molecular Biology Cell Proliferation Pharmacology Mice Inbred BALB C biology Cell growth Cyclin-Dependent Kinase 2 Cyclin-dependent kinase 2 Intracellular Signaling Peptides and Proteins MITOCHONDRIAL FERRITIN Cell Biology Iron metabolism G1 Phase Cell Cycle Checkpoints Cyclin Mitochondria Cell biology Cell culture Ferritins biology.protein Molecular Medicine Tumor Suppressor Protein p53 Research Article |
| Zdroj: | Cellular and Molecular Life Sciences |
| ISSN: | 1420-9071 1420-682X |
| Popis: | Mitochondrial ferritin (FtMt) has a significant effect on the regulation of cytosolic and mitochondrial iron levels. However, because of the deficiency of iron regulatory elements (IRE) in FtMt’s gene sequence, the exact function of FtMt remains unclear. In the present study, we found that FtMt dramatically inhibited SH-SY5Y cell proliferation and tumor growth in nude mice. Interestingly, excess FtMt did not adversely affect the development of drosophila. Additionally, we found that the expression of FtMt in human normal brain tissue was significantly higher than that of neuroblastoma, but not higher than that of neurospongioma. However, the expression of transferrin receptor 1 is completely opposite. We therefore hypothesized that increased expression of FtMt may negatively affect the vitality of neuronal tumor cells. Therefore, we further investigated the underlying mechanisms of FtMt’s inhibitory effects on neuronal tumor cell proliferation. As expected, FtMt overexpression disturbed the iron homeostasis of tumor cells and significantly downregulated the expression of proliferating cell nuclear antigen. Moreover, FtMt affected cell cycle, causing G1/S arrest by modifying the expression of cyclinD1, cyclinE, Cdk2, Cdk4 and p21. Remarkably, FtMt strongly upregulated the expression of the tumor suppressors, p53 and N-myc downstream-regulated gene-1 (NDRG1), but dramatically decreased C-myc, N-myc and p-Rb levels. This study demonstrates for the first time a new role and mechanism for FtMt in the regulation of cell cycle. We thus propose FtMt as a new candidate target for inhibiting neuronal tumor cell proliferation. Appropriate regulation of FtMt expression may prevent tumor cell growth. Our study may provide a new strategy for neuronal cancer therapy. Electronic supplementary material The online version of this article (doi:10.1007/s00018-014-1730-0) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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