NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth
| Autor: | Vladimir Shulaev, Luhua Song, Ron Mittler, Sarah H. Holt, Abraham Hochberg, Yang Sung Sohn, Rachel Nechushtai, José N. Onuchic, Andrea R. Conlan, Dorit Michaeli, Yael Harir, Imad Matouk, Sagi Tamir, Ioav Z. Cabanchick, Patricia A. Jennings, Mark L. Paddock |
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| Rok vydání: | 2013 |
| Předmět: |
Programmed cell death
Carcinogenesis Cell Survival Immunoblotting Transplantation Heterologous Mice Nude Breast Neoplasms Biology Mitochondrion medicine.disease_cause Mitochondrial Proteins Mice Microscopy Electron Transmission Cell Line Tumor Oxygen homeostasis medicine Animals Homeostasis Humans Cell Proliferation Membrane Potential Mitochondrial Multidisciplinary Pioglitazone Autophagy Membrane Proteins Cancer Biological Sciences medicine.disease Mitochondria Tumor Burden Cell biology Membrane protein Cancer cell MCF-7 Cells Female Oligomycins RNA Interference Thiazolidinediones Reactive Oxygen Species Glycolysis |
| Zdroj: | Proceedings of the National Academy of Sciences. 110:14676-14681 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1313198110 |
| Popis: | Mitochondria are emerging as important players in the transformation process of cells, maintaining the biosynthetic and energetic capacities of cancer cells and serving as one of the primary sites of apoptosis and autophagy regulation. Although several avenues of cancer therapy have focused on mitochondria, progress in developing mitochondria-targeting anticancer drugs nonetheless has been slow, owing to the limited number of known mitochondrial target proteins that link metabolism with autophagy or cell death. Recent studies have demonstrated that two members of the newly discovered family of NEET proteins, NAF-1 (CISD2) and mitoNEET (mNT; CISD1), could play such a role in cancer cells. NAF-1 was shown to be a key player in regulating autophagy, and mNT was proposed to mediate iron and reactive oxygen homeostasis in mitochondria. Here we show that the protein levels of NAF-1 and mNT are elevated in human epithelial breast cancer cells, and that suppressing the level of these proteins using shRNA results in significantly reduced cell proliferation and tumor growth, decreased mitochondrial performance, uncontrolled accumulation of iron and reactive oxygen in mitochondria, and activation of autophagy. Our findings highlight NEET proteins as promising mitochondrial targets for cancer therapy. |
| Databáze: | OpenAIRE |
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