ArticleCancer research2014
Plk1 inhibition enhances the efficacy of androgen signaling blockade in castration-resistant prostate cancer.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Androgen receptor variant-driven prostate cancer II: advances in clinical investigation.Prostate cancer and prostatic diseases · 2020Pooled it
- Black Phosphorus Nanosheets Induce Ferroptosis in Oral Squamous Cell Carcinoma via PI3K-AKT-SREBP1 Signaling Pathway-Mediated Lipogenesis.ACS omega · 2026Article
- Molecular mechanisms and classification of castration-resistant prostate cancer: Insights into androgen receptor, cancer stem cells, and neuroendocrine features.Current urology · 2026Article
- Intratumoral Androgens and Genetic Variants Driving Therapy Resistance in Prostate Cancer.Research (Washington, D.C.) · 2026Review
- Unravelling TPX2-centered co-expression networks as key drivers of aggressive prostate cancer.Scientific reports · 2025Article
- Mechanisms and pathways of ROS and autophagy in thyroid cancer.Future science OA · 2025Review
- Article
- PLK1 inhibition enhances gemcitabine-induced apoptosis through PLK1-dependent ERK1/2-Bim and AKT1/Noxa signals in pancreatic cancer cells.Medical oncology (Northwood, London, England) · 2025Article
- Cryptococcosis, tuberculosis, and a kidney cancer fail to fit the atherosclerosis paradigm for foam cell lipid content.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- The kinase PLK1 promotes Hedgehog signaling-dependent resistance to the antiandrogen enzalutamide in metastatic prostate cancer.Science signaling · 2025Article
- PLK1 phosphorylates WRN at replication forks.The Journal of pharmacology and experimental therapeutics · 2025Article
- AKT Inhibition Sensitizes to Polo-Like Kinase 1 Inhibitor Onvansertib in Prostate Cancer.Molecular cancer therapeutics · 2024Article
- Article
- Article
- MED15 is upregulated by HIF-2α and promotes proliferation and metastasis in clear cell renal cell carcinoma via activation of SREBP-dependent fatty acid synthesis.Cell death discovery · 2024Article
- Review
- PLK1: A Promising Therapeutic Target for Prostate Cancer Treatment.Serican journal of medicine · 2024Article
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- A kinome-wide CRISPR screen identifies CK1α as a target to overcome enzalutamide resistance of prostate cancer.Cell reports. Medicine · 2023Article
- Plk1 Inhibitors and Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling.Cancer research · 2023Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Prostate cancer is thought to be driven by oxidative stress, lipid metabolism, androgen receptor (AR) signaling, and activation of the PI3K-AKT-mTOR pathway, but it is uncertain how they may become coordinated during progression to castration-resistant disease that remains incurable. The mitotic kinase polo-like kinase 1 (Plk1) is elevated in prostate cancer, where its expression is linked to tumor grade. Notably, Plk1 signaling and lipid metabolism were identified recently as two of the top five most upregulated pathways in a mouse xenograft model of human prostate cancer. Herein, we show that oxidative stress activates both the PI3K-AKT-mTOR pathway and AR signaling in a Plk1-dependent manner in prostate cells. Inhibition of the PI3K-AKT-mTOR pathway prevented oxidative stress-induced activation of AR signaling. Plk1 modulation also affected cholesteryl ester accumulation in prostate cancer via the SREBP pathway. Finally, Plk1 inhibition enhanced cellular responses to androgen signaling inhibitors (ASI) and overcame ASI resistance in both cultured prostate cancer cells and patient-derived tumor xenografts. Given that activation of AR signaling and the PI3K-AKT-mTOR pathway is sufficient to elevate SREBP-dependent expression of key lipid biosynthesis enzymes in castration-resistant prostate cancer (CRPC), our findings argued that Plk1 activation was responsible for coordinating and driving these processes to promote and sustain the development of this advanced stage of disease. Overall, our results offer a strong mechanistic rationale to evaluate Plk1 inhibitors in combination drug trials to enhance the efficacy of ASIs in CRPC.
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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.