ArticleCancer research2016
AMPK Activation and Metabolic Reprogramming by Tamoxifen through Estrogen Receptor-Independent Mechanisms Suggests New Uses for This Therapeutic Modality in Cancer Treatment.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 95 citations in OpenAlex.
- Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis.Nature communications · 2023Trial
- Article
- Nano-/Nanobiotechnology-Augmented Pyroptosis in the Treatment of Triple-Negative Breast Cancer: An Updated Review.International journal of nanomedicine · 2026Review
- Empagliflozin demonstrates cytotoxicity and synergy with tamoxifen in ER-positive breast cancer cells: anti-proliferative and anti-survival effects.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Advancements in Nanocarrier Delivery Systems for Photodynamic Therapy in Lung Cancer.International journal of nanomedicine · 2025Review
- Correlating NAD(P)H lifetime shifts to tamoxifen resistance in breast cancer cells: A metabolic screening study with time-resolved flow cytometry.Journal of innovative optical health sciences · 2025Article
- Cancer Cells Show Higher Sensitivity to Melatonin-Tamoxifen Drug Conjugates than to Combination of Melatonin and Tamoxifen.ACS omega · 2024Article
- Inhibition of OXPHOS induces metabolic rewiring and reduces hypoxia in murine tumor models.Clinical and translational radiation oncology · 2024Article
- Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy.Acta pharmaceutica Sinica. B · 2024Article
- Mitochondria Energy Metabolism Depression as Novel Adjuvant to Sensitize Radiotherapy and Inhibit Radiation Induced-Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mitochondria-Targeted Nanoadjuvants Induced Multi-Functional Immune-Microenvironment Remodeling to Sensitize Tumor Radio-Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Autophagy and senescence facilitate the development of antiestrogen resistance in ER positive breast cancer.Frontiers in endocrinology · 2024Review
- Role of monocarboxylate transporter I/lactate dehydrogenase B-mediated lactate recycling in tamoxifen-resistant breast cancer cells.Archives of pharmacal research · 2023Article
- Unveiling the Anti-Cancer Potential of Onoceranoid Triterpenes fromInternational journal of molecular sciences · 2023Article
- Biodegradable nanoplatform upregulates tumor microenvironment acidity for enhanced cancer therapy via synergistic induction of apoptosis, ferroptosis, and anti-angiogenesis.Journal of nanobiotechnology · 2023Article
- Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer.Molecules (Basel, Switzerland) · 2023Review
- Review
- Estrogen-Related Receptor γ Maintains Pancreatic Acinar Cell Function and Identity by Regulating Cellular Metabolism.Gastroenterology · 2022Article
- Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets.Pharmaceutics · 2022Article
- Inhibition of Metabolism as a Therapeutic Option for Tamoxifen-Resistant Breast Cancer Cells.Cells · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Tamoxifen is the most widely used adjuvant chemotherapeutic for the treatment of estrogen receptor (ER)-positive breast cancer, yet a large body of clinical and preclinical data indicates that tamoxifen can modulate multiple cellular processes independently of ER status. Here, we describe the ER-independent effects of tamoxifen on tumor metabolism. Using combined pharmacologic and genetic knockout approaches, we demonstrate that tamoxifen inhibits oxygen consumption via inhibition of mitochondrial complex I, resulting in an increase in the AMP/ATP ratio and activation of the AMP-activated protein kinase (AMPK) signaling pathway in vitro and in vivo AMPK in turn promotes glycolysis and alters fatty acid metabolism. We also show that tamoxifen-induced cytotoxicity is modulated by isoform-specific effects of AMPK signaling, in which AMPKα1 promotes cell death through inhibition of the mTOR pathway and translation. By using agents that concurrently target distinct adaptive responses to tamoxifen-mediated metabolic reprogramming, we demonstrate increased cytotoxicity through synergistic therapeutic approaches. Our results demonstrate novel metabolic perturbations by tamoxifen in tumor cells, which can be exploited to expand the therapeutic potential of tamoxifen treatment beyond ER(+) breast cancer. Cancer Res; 76(11); 3295-306. ©2016 AACR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.