ArticleJournal of molecular cell biology2021
Fatty acid oxidation and autophagy promote endoxifen resistance and counter the effect of AKT inhibition in ER-positive breast cancer cells.
Article in Journal of molecular cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- AMPK-Mediated Lipid Metabolic Reprogramming in Cancer: From Mechanisms to Targeted Therapies.Cell biochemistry and function · 2026Review
- Decoding PARP roles in breast cancer therapy resistance.Molecular biology reports · 2026Review
- Mechanistic Links Between Obesity and Breast Cancer Progression: Cellular Crosstalk, Metabolic Reprogramming and Microenvironmental Drivers.Cell biochemistry and function · 2026Review
- Fatty Acid Metabolism in Health and Cancer: From Fundamental Mechanisms to Therapeutic Application.MedComm · 2026Review
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Expression analyses of fatty acid binding proteins (FABPs) in breast cancer subtypes: implications for immune modulation and clinical outcomes.Translational cancer research · 2026Article
- Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.Breast cancer (Dove Medical Press) · 2026Review
- Transcriptomic analysis identifies FABP5 as a candidate regulator of lipid accumulation in metabolic dysfunction-associated fatty liver disease.Frontiers in endocrinology · 2026Article
- Immune evasion driven by lipid metabolic reprogramming in endocrine-resistant HRFrontiers in immunology · 2026Review
- The role and mechanism of fatty acid oxidation in cancer drug resistance.Cell death discovery · 2025Review
- Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment.Molecular cancer · 2025Review
- A Hypothesized Therapeutic Role of (Z)-Endoxifen in Duchenne Muscular Dystrophy (DMD).Degenerative neurological and neuromuscular disease · 2025Article
- FGFR2-triggered autophagy and activation of Nrf-2 reduce breast cancer cell response to anti-ER drugs.Cellular & molecular biology letters · 2024Article
- Autophagy Modulation in Therapeutic Strategy of Breast Cancer Drug Resistance.Journal of Cancer · 2024Review
- Dysregulation of Fatty Acid Metabolism in Breast Cancer and Its Targeted Therapy.Breast cancer (Dove Medical Press) · 2024Review
- Review
- Targeting c-Jun inhibits fatty acid oxidation to overcome tamoxifen resistance in estrogen receptor-positive breast cancer.Cell death & disease · 2023Article
- Bone Marrow Mesenchymal Stem Cells Induce Metabolic Plasticity in Estrogen Receptor-Positive Breast Cancer.Molecular cancer research : MCR · 2023Article
- Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma.Journal of Zhejiang University. Science. B · 2023Article
- NAT10: An RNA cytidine transferase regulates fatty acid metabolism in cancer cells.Clinical and translational medicine · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Tamoxifen (TAM) is the first-line endocrine therapy for estrogen receptor-positive (ER+) breast cancer (BC). However, acquired resistance occurs in ∼50% cases. Meanwhile, although the PI3K/AKT/mTOR pathway is a viable target for treatment of endocrine therapy-refractory patients, complex signaling feedback loops exist, which can counter the effectiveness of inhibitors of this pathway. Here, we analyzed signaling pathways and metabolism in ER+ MCF7 BC cell line and their TAM-resistant derivatives that are co-resistant to endoxifen using immunoblotting, quantitative polymerase chain reaction, and the Agilent Seahorse XF Analyzer. We found that activation of AKT and the energy-sensing kinase AMPK was increased in TAM and endoxifen-resistant cells. Furthermore, ERRα/PGC-1β and their target genes MCAD and CPT-1 were increased and regulated by AMPK, which coincided with increased fatty acid oxidation (FAO) and autophagy in TAM-resistant cells. Inhibition of AKT feedback-activates AMPK and ERRα/PGC-1β-MCAD/CPT-1 with a consequent increase in FAO and autophagy that counters the therapeutic effect of endoxifen and AKT inhibitors. Therefore, our results indicate increased activation of AKT and AMPK with metabolic reprogramming and increased autophagy in TAM-resistant cells. Simultaneous inhibition of AKT and FAO/autophagy is necessary to fully sensitize resistant cells to endoxifen.
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