ArticlePloS one2015
Inhibition of Aerobic Glycolysis Represses Akt/mTOR/HIF-1α Axis and Restores Tamoxifen Sensitivity in Antiestrogen-Resistant Breast Cancer Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 126 citations in OpenAlex.
- Non-coding RNA-mediated mechanisms underlying tamoxifen resistance in breast cancer.Discover oncology · 2026Review
- The Warburg Effect and Aerobic Glycolysis in Tumors.Cancer treatment and research · 2026Review
- Aberrant activation of the PI3K/AKT/HIF‑1α pathway promotes glycolysis and lenvatinib resistance in liver cancer.Molecular medicine reports · 2025Article
- EDIL3 alleviates Mannan-induced psoriatic arthritis by slowing the intracellular glycolysis process in mononuclear-derived dendritic cells.Inflammation · 2025Article
- Computational modeling of cancer cell metabolism along the catabolic-anabolic axes.NPJ systems biology and applications · 2025Article
- miRNA-dependent resistance mechanisms to anti-hormonal therapies in estrogen receptor-positive breast cancer patients.Molecular therapy. Oncology · 2025Review
- Targeting Glycolysis for Treatment of Breast Cancer Resistance: Current Progress and Future Prospects.International journal of biological sciences · 2025Review
- Physical activity and glioblastoma: a paradigm shift in neuro-oncology therapy.Frontiers in oncology · 2025Review
- Programmed Cell Death of Chondrocytes, Synovial Cells, Osteoclasts, and Subchondral Bone Cells in Osteoarthritis.Journal of inflammation research · 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
- Article
- Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2.Nature communications · 2024Article
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Peptide set test: a peptide-centric strategy to infer differentially expressed proteins.Bioinformatics (Oxford, England) · 2024Article
- Drug resistance mechanisms in cancers: Execution of pro-survival strategies.Journal of biomedical research · 2024Article
- Mechanistic target of rapamycin in regulating macrophage function in inflammatory cardiovascular diseases.Journal of molecular and cellular cardiology · 2024Review
- Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine.Journal of advanced research · 2024Review
- Role of monocarboxylate transporter I/lactate dehydrogenase B-mediated lactate recycling in tamoxifen-resistant breast cancer cells.Archives of pharmacal research · 2023Article
- Roles of salt‑inducible kinases in cancer (Review).International journal of oncology · 2023Review
- The Significance of Microenvironmental and Circulating Lactate in Breast Cancer.International journal of molecular sciences · 2023Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tamoxifen resistance is often observed in the majority of estrogen receptor-positive breast cancers and it remains as a serious clinical problem in breast cancer management. Increased aerobic glycolysis has been proposed as one of the mechanisms for acquired resistance to chemotherapeutic agents in breast cancer cells such as adriamycin. Herein, we report that the glycolysis rates in LCC2 and LCC9--tamoxifen-resistant human breast cancer cell lines derived from MCF7--are higher than those in MCF7S, which is the parent MCF7 subline. Inhibition of key glycolytic enzyme such as hexokinase-2 resulted in cell growth retardation at higher degree in LCC2 and LCC9 than that in MCF7S. This implies that increased aerobic glycolysis even under O2-rich conditions, a phenomenon known as the Warburg effect, is closely associated with tamoxifen resistance. We found that HIF-1α is activated via an Akt/mTOR signaling pathway in LCC2 and LCC9 cells without hypoxic condition. Importantly, specific inhibition of hexokinase-2 suppressed the activity of Akt/mTOR/HIF-1α axis in LCC2 and LCC9 cells. In addition, the phosphorylated AMPK which is a negative regulator of mTOR was decreased in LCC2 and LCC9 cells compared to MCF7S. Interestingly, either the inhibition of mTOR activity or increase in AMPK activity induced a reduction in lactate accumulation and cell survival in the LCC2 and LCC9 cells. Taken together, our data provide evidence that development of tamoxifen resistance may be driven by HIF-1α hyperactivation via modulation of Akt/mTOR and/or AMPK signaling pathways. Therefore, we suggest that the HIF-1α hyperactivation is a critical marker of increased aerobic glycolysis in accordance with tamoxifen resistance and thus restoration of aerobic glycolysis may be novel therapeutic target for treatment of tamoxifen-resistant breast cancer.
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