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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
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Citations to this article in year 2017 (17)

Title and authors Publication Year
Mitochondrial Metabolism: Yin and Yang for Tumor Progression
L Valcarcel-Jimenez, E Gaude, V Torrano, C Frezza, A Carracedo
Trends in endocrinology and metabolism: TEM 2017
Mitochondrial toxicity of tobacco smoke and air pollution
JL Fetterman, MJ Sammy, SW Ballinger
Toxicology 2017
Expanding perspectives on the significance of mitophagy in cancer
LE Drake, MZ Springer, LP Poole, CJ Kim, KF Macleod
Seminars in Cancer Biology 2017
From discovery of the CHOP axis and targeting ClpP to the identification of additional axes of the UPRmt driven by the estrogen receptor and SIRT3
TC Kenny, D Germain
Journal of Bioenergetics and Biomembranes 2017
SIRT6 Suppresses Cancer Stem-like Capacity in Tumors with PI3K Activation Independently of Its Deacetylase Activity
RM Ioris, M Galié, G Ramadori, JG Anderson, A Charollais, G Konstantinidou, X Brenachot, E Aras, A Goga, N Ceglia, C Sebastián, D Martinvalet, R Mostoslavsky, P Baldi, R Coppari
Cell Reports 2017
Selected mitochondrial DNA landscapes activate the SIRT3 axis of the UPRmt to promote metastasis
TC Kenny, P Hart, M Ragazzi, M Sersinghe, J Chipuk, MA Sagar, KW Eliceiri, T LaFramboise, S Grandhi, J Santos, AK Riar, L Papa, M D'Aurello, G Manfredi, MG Bonini, D Germain
Oncogene 2017
Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells
ES Hwang, SB Song
Cellular and Molecular Life Sciences 2017
mtDNA, Metastasis, and the Mitochondrial Unfolded Protein Response (UPRmt)
TC Kenny, D Germain
Frontiers in Cell and Developmental Biology 2017
The Mitochondrial Complex(I)ty of Cancer
FA Urra, F Muñoz, A Lovy, C Cárdenas
Frontiers in Oncology 2017
Using Fractional Intensities of Time-resolved Fluorescence to Sensitively Quantify NADH/NAD+ with Genetically Encoded Fluorescent Biosensors
M Chang, L Li, H Hu, Q Hu, A Wang, X Cao, X Yu, S Zhang, Y Zhao, J Chen, Y Yang, J Xu
Scientific Reports 2017
The PWWP domain of the human oncogene WHSC1L1/NSD3 induces a metabolic shift toward fermentation
GB Rona, DS Almeida, AS Pinheiro, EC Eleutherio
Oncotarget 2017
Uncoupling genotoxic stress responses from circadian control increases susceptibility to mammary carcinogenesis
M Fang, PA Strickland, HG Kang, H Zarbl
Oncotarget 2017
Integrating the UPR mt into the mitochondrial maintenance network
CJ Fiorese, CM Haynes
Critical Reviews in Biochemistry and Molecular Biology 2017
Association of predicted pathogenic mutations in mitochondrial ND genes with distant metastasis in NSCLC and colon cancer
N Koshikawa, M Akimoto, JI Hayashi, H Nagase, K Takenaga
Scientific Reports 2017
An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers
SE Airhart, LM Shireman, LJ Risler, GD Anderson, GA Gowda, D Raftery, R Tian, DD Shen, KD OBrien, DA Sinclair
PloS one 2017
CD38 knockout suppresses tumorigenesis in mice and clonogenic growth of human lung cancer cells
X Bu, J Kato, JA Hong, MJ Merino, DS Schrump, FE Lund, J Moss
Carcinogenesis 2017
Mitochondrial Haplotype Alters Mammary Cancer Tumorigenicity and Metastasis in an Oncogenic Driver–Dependent Manner
AE Brinker, CJ Vivian, DC Koestler, TT Tsue, RA Jensen, DR Welch
Cancer research 2017

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