Downregulation of the Mitochondrial Phosphatase PTPMT1 Is Sufficient to Promote Cancer Cell Death
| العنوان: | Downregulation of the Mitochondrial Phosphatase PTPMT1 Is Sufficient to Promote Cancer Cell Death |
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| المؤلفون: | Natalie M. Niemi, Nathan J. Lanning, Laura M. Westrate, Jeffrey P. MacKeigan |
| المصدر: | PLoS ONE PLoS ONE, Vol 8, Iss 1, p e53803 (2013) |
| بيانات النشر: | Public Library of Science, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | lcsh:Medicine, Mitochondrion, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Adenosine Triphosphate, Neoplasms, Drug Discovery, Molecular Cell Biology, Basic Cancer Research, Cardiolipin, lcsh:Science, Energy-Producing Organelles, 0303 health sciences, Multidisciplinary, biology, Cell Death, Lipids, Cell biology, Enzymes, Mitochondria, Gene Expression Regulation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, Medicine, Research Article, Signal Transduction, Programmed cell death, Paclitaxel, Cardiolipins, Phosphatase, Bioenergetics, Cell Growth, 03 medical and health sciences, Downregulation and upregulation, Dual-specificity phosphatase, Genetics, Humans, Gene Silencing, Biology, 030304 developmental biology, lcsh:R, PTEN Phosphohydrolase, chemistry, Apoptosis, Cancer cell, biology.protein, lcsh:Q, Gene Function, HeLa Cells |
| الوصف: | Protein Tyrosine Phosphatase localized to the Mitochondrion 1 (PTPMT1) is a dual specificity phosphatase exclusively localized to the mitochondria, and has recently been shown to be a critical component in the cardiolipin biosynthetic pathway. The downregulation of PTPMT1 in pancreatic beta cells has been shown to increase cellular ATP levels and insulin production, however, the generalized role of PTPMT1 in cancer cells has not been characterized. Here we report that downregulation of PTPMT1 activity is sufficient to induce apoptosis of cancer cells. Additionally, the silencing of PTPMT1 decreases cardiolipin levels in cancer cells, while selectively increasing ATP levels in glycolytic media. Additionally, sublethal downregulation of PTPMT1 synergizes with low doses of paclitaxel to promote cancer cell death. Our data suggest that inhibition of PTPMT1 causes a metabolic crisis in cancer cells that induces cell death, and may be a mechanism by which cancer cells can be sensitized to currently available therapies. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2865f9bc8022bdfe2560cfd8888de939Test http://europepmc.org/articles/PMC3542197Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2865f9bc8022bdfe2560cfd8888de939 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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