Difference between revisions of "Santidrian 2013 J Clin Invest"
(Created page with "{{Publication |title=Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, Leboeuf SE, Gay LJ, Yagi T, Felding-Habermann B (2013) Mitochondrial complex I activity and NAD+/NADH balan...") Β |
|||
Line 1: | Line 1: | ||
{{Publication | {{Publication | ||
|title=Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, Leboeuf SE, Gay LJ, Yagi T, Felding-Habermann B (2013) Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression. J Clin Invest [Epub ahead of print]. Β | |title=Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, Leboeuf SE, Gay LJ, Yagi T, Felding-Habermann B (2013) Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression. J Clin Invest [Epub ahead of print]. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/23426180 PMID: 23426180] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/23426180 PMID: 23426180 Open Access] | ||
|authors=Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, Leboeuf SE, Gay LJ, Yagi T, Felding-Habermann B | |authors=Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, Leboeuf SE, Gay LJ, Yagi T, Felding-Habermann B | ||
|year=2013 | |year=2013 | ||
|journal=J Clin Invest | |journal=J Clin Invest | ||
|abstract=Despite advances in clinical therapy, metastasis remains the leading cause of death in breast cancer patients. Mutations in mitochondrial DNA, including those affecting complex I and oxidative phosphorylation, are found in breast tumors and could facilitate metastasis. This study identifies mitochondrial complex I as critical for defining an aggressive phenotype in breast cancer cells. Specific enhancement of mitochondrial complex I activity inhibited tumor growth and metastasis through regulation of the tumor cell NAD+/NADH redox balance, mTORC1 activity, and autophagy. Conversely, nonlethal reduction of NAD+ levels by interfering with nicotinamide phosphoribosyltransferase expression rendered tumor cells more aggressive and increased metastasis. The results translate into a new therapeutic strategy: enhancement of the NAD+/NADH balance through treatment with NAD+ precursors inhibited metastasis in xenograft models, increased animal survival, and strongly interfered with oncogene-driven breast cancer progression in the MMTV-PyMT mouse model. Thus, aberration in mitochondrial complex I NADH dehydrogenase activity can profoundly enhance the aggressiveness of human breast cancer cells, while therapeutic normalization of the NAD+/NADH balance can inhibit metastasis and prevent disease progression. | |abstract=Despite advances in clinical therapy, metastasis remains the leading cause of death in breast cancer patients. Mutations in mitochondrial DNA, including those affecting complex I and oxidative phosphorylation, are found in breast tumors and could facilitate metastasis. This study identifies mitochondrial complex I as critical for defining an aggressive phenotype in breast cancer cells. Specific enhancement of mitochondrial complex I activity inhibited tumor growth and metastasis through regulation of the tumor cell NAD+/NADH redox balance, mTORC1 activity, and autophagy. Conversely, nonlethal reduction of NAD+ levels by interfering with nicotinamide phosphoribosyltransferase expression rendered tumor cells more aggressive and increased metastasis. The results translate into a new therapeutic strategy: enhancement of the NAD+/NADH balance through treatment with NAD+ precursors inhibited metastasis in xenograft models, increased animal survival, and strongly interfered with oncogene-driven breast cancer progression in the MMTV-PyMT mouse model. Thus, aberration in mitochondrial complex I NADH dehydrogenase activity can profoundly enhance the aggressiveness of human breast cancer cells, while therapeutic normalization of the NAD+/NADH balance can inhibit metastasis and prevent disease progression. | ||
|keywords=Metastasis, NAD+/NADH redox balance, mTORC1, Autophagy, Β | |keywords=Metastasis, NAD+/NADH redox balance, mTORC1, Autophagy, | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
Line 13: | Line 13: | ||
|organism=Mouse | |organism=Mouse | ||
|preparations=Intact Cell; Cultured; Primary | |preparations=Intact Cell; Cultured; Primary | ||
|couplingstates=ROUTINE | |||
|enzymes=Complex I, Complex III | |enzymes=Complex I, Complex III | ||
}} | }} |
Revision as of 10:27, 26 February 2013
Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, Leboeuf SE, Gay LJ, Yagi T, Felding-Habermann B (2013) Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression. J Clin Invest [Epub ahead of print]. |
Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, Leboeuf SE, Gay LJ, Yagi T, Felding-Habermann B (2013) J Clin Invest
Abstract: Despite advances in clinical therapy, metastasis remains the leading cause of death in breast cancer patients. Mutations in mitochondrial DNA, including those affecting complex I and oxidative phosphorylation, are found in breast tumors and could facilitate metastasis. This study identifies mitochondrial complex I as critical for defining an aggressive phenotype in breast cancer cells. Specific enhancement of mitochondrial complex I activity inhibited tumor growth and metastasis through regulation of the tumor cell NAD+/NADH redox balance, mTORC1 activity, and autophagy. Conversely, nonlethal reduction of NAD+ levels by interfering with nicotinamide phosphoribosyltransferase expression rendered tumor cells more aggressive and increased metastasis. The results translate into a new therapeutic strategy: enhancement of the NAD+/NADH balance through treatment with NAD+ precursors inhibited metastasis in xenograft models, increased animal survival, and strongly interfered with oncogene-driven breast cancer progression in the MMTV-PyMT mouse model. Thus, aberration in mitochondrial complex I NADH dehydrogenase activity can profoundly enhance the aggressiveness of human breast cancer cells, while therapeutic normalization of the NAD+/NADH balance can inhibit metastasis and prevent disease progression. β’ Keywords: Metastasis, NAD+/NADH redox balance, mTORC1, Autophagy
Labels:
Stress:Cancer; Apoptosis; Cytochrome c"Cancer; Apoptosis; Cytochrome c" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Mouse
Preparation: Intact Cell; Cultured; Primary"Intact Cell; Cultured; Primary" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property. Enzyme: Complex I, Complex III
Coupling state: ROUTINE
HRR: Oxygraph-2k