ArticleCancer research2021
Supraphysiologic Testosterone Induces Ferroptosis and Activates Immune Pathways through Nucleophagy in Prostate Cancer.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 46 citations in OpenAlex.
- Bipolar androgen therapy plus nivolumab for patients with metastatic castration-resistant prostate cancer: the COMBAT phase II trial.Nature communications · 2024Trial
- Ferroptosis at the Metabolic-Immune Interface in Metastatic Castration-Resistant Prostate Cancer: Mechanistic Evidence, Translational Gaps, and Combination Strategies.Annals of surgical oncology · 2026Review
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Ferroptosis and prostate cancer: A translational path from molecular mechanisms to precision therapy.Genes & diseases · 2026Review
- The role of the cGAS-STING pathway in male reproductive disorders.Molecular biology reports · 2026Review
- Emerging therapies to overcome antiandrogen resistance and beyond in lethal prostate cancer.Journal of the National Cancer Center · 2026Review
- Androgen receptor signaling organizes ferroptosis escape in castration-resistant prostate cancer: a threshold-based model for therapeutic timing.Frontiers in oncology · 2026Review
- Systematic pan-cancer analysis identified NCOA4 as an immunological and prognostic biomarker and validated in lung adenocarcinoma.Discover oncology · 2025Article
- Mammalian nucleophagy: process and function.Autophagy · 2025Review
- Tracing the Evolution of Sex Hormones and Receptor-Mediated Immune Microenvironmental Differences in Prostate and Bladder Cancers: From Embryonic Development to Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Targeting ferroptosis in prostate cancer management: molecular mechanisms, multidisciplinary strategies and translational perspectives.Journal of translational medicine · 2025Review
- Sex bias in tumor immunity: insights from immune cells.Theranostics · 2025Review
- The Innate Immune System and the TRAIL-Bcl-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females.Cancer research · 2024Article
- Mechanisms of ferroptosis and targeted therapeutic approaches in urological malignancies.Cell death discovery · 2024Review
- Arsenic-Induced Ferroptosis in Chicken Hepatocytes via the Mitochondrial ROS Pathway.Biological trace element research · 2024Article
- Sequence of androgen receptor-targeted vaccination with androgen deprivation therapy affects anti-prostate tumor efficacy.Journal for immunotherapy of cancer · 2024Article
- Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS.Human reproduction open · 2024Article
- Ferritinophagy: research advance and clinical significance in cancers.Cell death discovery · 2023Review
- The constructive and destructive impact of autophagy on both genders' reproducibility, a comprehensive review.Autophagy · 2023Review
- Decoding the Influence of Obesity on Prostate Cancer and Its Transgenerational Impact.Nutrients · 2023Review
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25 authors at 2 institutions in 2 countries.
Funding
Abstract
The discovery that androgens play an important role in the progression of prostate cancer led to the development of androgen deprivation therapy (ADT) as a first line of treatment. However, paradoxical growth inhibition has been observed in a subset of prostate cancer upon administration of supraphysiologic levels of testosterone (SupraT), both experimentally and clinically. Here we report that SupraT activates cytoplasmic nucleic acid sensors and induces growth inhibition of SupraT-sensitive prostate cancer cells. This was initiated by the induction of two parallel autophagy-mediated processes, namely, ferritinophagy and nucleophagy. Consequently, autophagosomal DNA activated nucleic acid sensors converge on NFκB to drive immune signaling pathways. Chemokines and cytokines secreted by the tumor cells in response to SupraT resulted in increased migration of cytotoxic immune cells to tumor beds in xenograft models and patient tumors. Collectively, these findings indicate that SupraT may inhibit a subset of prostate cancer by activating nucleic acid sensors and downstream immune signaling. SIGNIFICANCE: This study demonstrates that supraphysiologic testosterone induces two parallel autophagy-mediated processes, ferritinophagy and nucleophagy, which then activate nucleic acid sensors to drive immune signaling pathways in 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.