ArticleOncotarget2016
Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 79 citations in OpenAlex.
- Article
- Loss of ATP-Dependent Citrate Lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling.Circulation · 2026Article
- Histone modifications across cancers: mechanisms, therapy and clinical translation.Molecular cancer · 2026Review
- De Novo Lipogenesis in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Rewired lipid metabolism in castration-resistant prostate cancer: molecular interplay between glucose metabolism and sterol synthesis.Molecular biology reports · 2026Review
- Identifying myosin heavy chain 11 as a predictive biomarker of prostate cancer progression and antiandrogen resistance.Oncology letters · 2026Article
- Exploring the significance of fatty acid metabolism reprogramming in the pathogenesis of cancer and anticancer therapy.Annals of medicine · 2025Review
- Reprogrammed Lipid Metabolism-Associated Therapeutic Vulnerabilities in Prostate Cancer.International journal of molecular sciences · 2025Review
- Matairesinol Targets Lipid Metabolism Reprogramming in AR-Independent Prostate Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Metabolic Adaptations in Cancer Progression: Optimization Strategies and Therapeutic Targets.Cancers · 2025Review
- Targeting Prostate Cancer Metabolism Through Transcriptional and Epigenetic Modulation: A Multi-Target Approach to Therapeutic Innovation.International journal of molecular sciences · 2025Review
- Beta-blockers prolong response to androgen deprivation therapy in prostate cancer through modulation of the neuro-immuno-oncology axis.Journal of translational medicine · 2025Article
- A feedforward loop between ACLY and MYC supports T-ALL progression in vivo.Blood neoplasia · 2025Article
- Review
- Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis.Cell reports · 2025Article
- Noncanonical TCA cycle fosters canonical TCA cycle and mitochondrial integrity in acute myeloid leukemia.Cancer science · 2025Article
- The role of DGAT1 and DGAT2 in regulating tumor cell growth and their potential clinical implications.Journal of translational medicine · 2024Review
- SIRT2-mediated deacetylation of ACLY promotes the progression of oesophageal squamous cell carcinoma.Journal of cellular and molecular medicine · 2024Article
- Role ofQuantitative biology (Beijing, China) · 2024Article
- Prostate-Specific Membrane Antigen (PSMA) Expression Predicts Need for Early Treatment in Prostate Cancer Patients Managed with Active Surveillance.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The androgen receptor (AR) plays a central role in prostate tumor growth. Inappropriate reactivation of the AR after androgen deprivation therapy promotes development of incurable castration-resistant prostate cancer (CRPC). In this study, we provide evidence that metabolic features of prostate cancer cells can be exploited to sensitize CRPC cells to AR antagonism. We identify a feedback loop between ATP-citrate lyase (ACLY)-dependent fatty acid synthesis, AMPK, and the AR in prostate cancer cells that could contribute to therapeutic resistance by maintaining AR levels. When combined with an AR antagonist, ACLY inhibition in CRPC cells promotes energetic stress and AMPK activation, resulting in further suppression of AR levels and target gene expression, inhibition of proliferation, and apoptosis. Supplying exogenous fatty acids can restore energetic homeostasis; however, this rescue does not occur through increased β-oxidation to support mitochondrial ATP production. Instead, concurrent inhibition of ACLY and AR may drive excess ATP consumption as cells attempt to cope with endoplasmic reticulum (ER) stress, which is prevented by fatty acid supplementation. Thus, fatty acid metabolism plays a key role in coordinating ER and energetic homeostasis in CRPC cells, thereby sustaining AR action and promoting proliferation. Consistent with a role for fatty acid metabolism in sustaining AR levels in prostate cancer in vivo, AR mRNA levels in human prostate tumors correlate positively with expression of ACLY and other fatty acid synthesis genes. The ACLY-AMPK-AR network can be exploited to sensitize CRPC cells to AR antagonism, suggesting novel therapeutic opportunities for prostate cancer.
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Registered trials
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.