ArticleMolecular and cellular biology2015
Cotargeting Polo-Like Kinase 1 and the Wnt/β-Catenin Signaling Pathway in Castration-Resistant Prostate Cancer.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- PLK1: A Promising Therapeutic Target for Prostate Cancer Treatment.Serican journal of medicine · 2024Article
- CDC20 Is Regulated by the Histone Methyltransferase, KMT5A, in Castration-Resistant Prostate Cancer.Cancers · 2023Article
- From Basic Science to Clinical Practice: The Role of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A)/p90 in Cancer.Frontiers in genetics · 2023Review
- Diptoindonesin G antagonizes AR signaling and enhances the efficacy of antiandrogen therapy in prostate cancer.The Prostate · 2022Article
- Choosing Kinase Inhibitors for Androgen Deprivation Therapy-Resistant Prostate Cancer.Pharmaceutics · 2022Review
- Exploring the Wnt Pathway as a Therapeutic Target for Prostate Cancer.Biomolecules · 2022Review
- Wnt16 signaling in bone homeostasis and osteoarthristis.Frontiers in endocrinology · 2022Review
- CDC20 is a novel biomarker for improved clinical predictions in epithelial ovarian cancer.American journal of cancer research · 2022Article
- Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses.Cell discovery · 2021Review
- Review
- The Identification of Stemness-Related Genes in the Risk of Head and Neck Squamous Cell Carcinoma.Frontiers in oncology · 2021Article
- Epigenetic regulation of prostate cancer.Genes & diseases · 2020Review
- PLK1 regulates hepatic stellate cell activation and liver fibrosis through Wnt/β-catenin signalling pathway.Journal of cellular and molecular medicine · 2020Article
- Crosstalk Between AR and Wnt Signaling Promotes Castration-Resistant Prostate Cancer Growth.OncoTargets and therapy · 2020Article
- Plk1 Inhibition Enhances the Efficacy of BET Epigenetic Reader Blockade in Castration-Resistant Prostate Cancer.Molecular cancer therapeutics · 2018Article
- Single-Cell RNA-seq Reveals a Subpopulation of Prostate Cancer Cells with Enhanced Cell-Cycle-Related Transcription and Attenuated Androgen Response.Cancer research · 2018Article
- Recent advances on the progressive mechanism and therapy in castration-resistant prostate cancer.OncoTargets and therapy · 2018Review
- Review
- Targeting Plk1 to Enhance Efficacy of Olaparib in Castration-Resistant Prostate Cancer.Molecular cancer therapeutics · 2017Article
- ST6Gal-I overexpression facilitates prostate cancer progression via the PI3K/Akt/GSK-3β/β-catenin signaling pathway.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
The Wnt/β-catenin signaling pathway has been identified as one of the predominantly upregulated pathways in castration-resistant prostate cancer (CRPC). However, whether targeting the β-catenin pathway will prove effective as a CRPC treatment remains unknown. Polo-like kinase 1 (Plk1) is a critical regulator in many cell cycle events, and its level is significantly elevated upon castration of mice carrying xenograft prostate tumors. Indeed, inhibition of Plk1 has been shown to inhibit tumor growth in several in vivo studies. Here, we show that Plk1 is a negative regulator of Wnt/β-catenin signaling. Plk1 inhibition or depletion enhances the level of cytosolic and nuclear β-catenin in human prostate cancer cells. Furthermore, inhibition of Wnt/β-catenin signaling significantly potentiates the antineoplastic activity of the Plk1 inhibitor BI2536 in both cultured prostate cancer cells and CRPC xenograft tumors. Mechanistically, axin2, a negative regulator of the β-catenin pathway, serves as a substrate of Plk1, and Plk1 phosphorylation of axin2 facilitates the degradation of β-catenin by enhancing binding between glycogen synthase kinase 3β (GSK3β) and β-catenin. Plk1-phosphorylated axin2 also exhibits resistance to Cdc20-mediated degradation. Overall, this study identifies a novel Plk1-Wnt signaling axis in prostate cancer, offering a promising new therapeutic option to treat CRPC.
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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.