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Citations to this article

Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression
Antonio F. Santidrian, … , Takao Yagi, Brunhilde Felding-Habermann
Antonio F. Santidrian, … , Takao Yagi, Brunhilde Felding-Habermann
Published February 15, 2013
Citation Information: J Clin Invest. 2013;123(3):1068-1081. https://doi.org/10.1172/JCI64264.
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Research Article Oncology Article has an altmetric score of 26

Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression

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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.

Authors

Antonio F. Santidrian, Akemi Matsuno-Yagi, Melissa Ritland, Byoung B. Seo, Sarah E. LeBoeuf, Laurie J. Gay, Takao Yagi, Brunhilde Felding-Habermann

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2009 Total
Citations: 9 15 16 28 20 17 16 12 17 13 23 20 8 1 215
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2018 (12)

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Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence
L Rajman, K Chwalek, DA Sinclair
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D Jia, J Park, K Jung, H Levine, B Kaipparettu
Cells 2018
Cytochrome C oxidase Inhibition and Cold Plasma-derived Oxidants Synergize in Melanoma Cell Death Induction
RK Gandhirajan, K Rödder, Y Bodnar, G Pasqual-Melo, S Emmert, CE Griguer, KD Weltmann, S Bekeschus
Scientific Reports 2018
The Oncojanus Paradigm of Respiratory Complex I
G Leone, H Abla, G Gasparre, A Porcelli, L Iommarini
Genes & development 2018
Profiling Redox and Energy Coenzymes in Whole Blood, Tissue and Cells Using NMR Spectroscopy
G Gowda
Metabolites 2018
Oxygen Transport to Tissue XL
O Thews, JC LaManna, DK Harrison
2018
Ribosomal protein L10 in mitochondria serves as a regulator for ROS level in pancreatic cancer cells
J Yang, Z Chen, N Liu, Y Chen
Redox Biology 2018
TIMMDC1 Knockdown Inhibits Growth and Metastasis of Gastric Cancer Cells Through Metabolic Inhibition and AKT/GSK3β/β-Catenin Signaling Pathway
Y Liu, Y Huang, J Zhang, C Pei, J Hu, J Lyu, Y Shen
International journal of biological sciences 2018
Decreased NAD Activates STAT3 and Integrin Pathways to Drive Epithelial-Mesenchymal Transition
W Wang, Y Hu, C Yang, S Zhu, X Wang, Z Zhang, H Deng
Molecular & cellular proteomics : MCP 2018
Uncoupling protein 3 deficiency impairs myocardial fatty acid oxidation and contractile recovery following ischemia/reperfusion
KS Edwards, S Ashraf, TM Lomax, JM Wiseman, ME Hall, FN Gava, JE Hall, JP Hosler, R Harmancey
Basic Research in Cardiology 2018
Integrated landscape of copy number variation and RNA expression associated with nodal metastasis in invasive ductal breast carcinoma
M Behring, S Shrestha, U Manne, X Cui, A Gonzalez-Reymundez, A Grueneberg, AI Vazquez
Oncotarget 2018
A risk assessment model for the prognosis of osteosarcoma utilizing differentially expressed lncRNAs
K Sun, J Zhao
Molecular medicine reports 2018

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