ArticleMolecular cancer therapeutics2014
Pharmacologic suppression of JAK1/2 by JAK1/2 inhibitor AZD1480 potently inhibits IL-6-induced experimental prostate cancer metastases formation.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Review
- Article
- Stat5 induces androgen receptor (Science advances · 2024Article
- Review
- AT-rich interaction domain 5A regulates the transcription of interleukin-6 gene in prostate cancer cells.The Prostate · 2022Article
- Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?Cancers · 2021Review
- Impact of STAT Proteins in Tumor Progress and Therapy Resistance in Advanced and Metastasized Prostate Cancer.Cancers · 2021Review
- Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells.Journal of cellular and molecular medicine · 2021Article
- Targeting Intercellular Communication in the Bone Microenvironment to Prevent Disseminated Tumor Cell Escape from Dormancy and Bone Metastatic Tumor Growth.International journal of molecular sciences · 2021Review
- Novel Combinatorial Approaches to Tackle the Immunosuppressive Microenvironment of Prostate Cancer.Cancers · 2021Review
- Tumor Evolution in a Patient with Recurrent Endometrial Cancer and Synchronous Neuroendocrine Cancer and Response to Checkpoint Inhibitor Treatment.The oncologist · 2021Article
- Recent Advances in the Role of Arid5a in Immune Diseases and Cancer.Frontiers in immunology · 2021Review
- Cytokines and Chemokines as Mediators of Prostate Cancer Metastasis.International journal of molecular sciences · 2020Review
- Targeting STAT-3 signaling pathway in cancer for development of novel drugs: Advancements and challenges.Genetics and molecular biology · 2020Article
- Microarray expression profiles analysis revealed lncRNA OXCT1-AS1 promoted bladder cancer cell aggressiveness via miR-455-5p/JAK1 signaling.Journal of cellular physiology · 2019Article
- Downregulation of Pro-Inflammatory and Pro-Angiogenic Pathways in Prostate Cancer Cells by a Polyphenol-Rich Extract from Olive Mill Wastewater.International journal of molecular sciences · 2019Article
- ATM‑JAK‑PD‑L1 signaling pathway inhibition decreases EMT and metastasis of androgen‑independent prostate cancer.Molecular medicine reports · 2018Article
- Inhibition of IL-6-JAK/Stat3 signaling in castration-resistant prostate cancer cells enhances the NK cell-mediated cytotoxicity via alteration of PD-L1/NKG2D ligand levels.Molecular oncology · 2018Article
- The Role and Mechanism of Epithelial-to-Mesenchymal Transition in Prostate Cancer Progression.International journal of molecular sciences · 2017Review
- Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
Metastatic prostate cancer is lethal and lacks effective strategies for prevention or treatment, requiring novel therapeutic approaches. Interleukin-6 (IL-6) is a cytokine that has been linked with prostate cancer pathogenesis by multiple studies. However, the direct functional roles of IL-6 in prostate cancer growth and progression have been unclear. In the present study, we show that IL-6 is produced in distant metastases of clinical prostate cancers. IL-6-activated signaling pathways in prostate cancer cells induced a robust 7-fold increase in metastases formation in nude mice. We further show that IL-6 promoted migratory prostate cancer cell phenotype, including increased prostate cancer cell migration, microtubule reorganization, and heterotypic adhesion of prostate cancer cells to endothelial cells. IL-6-driven metastasis was predominantly mediated by Stat3 and to lesser extent by ERK1/2. Most importantly, pharmacologic inhibition of Jak1/2 by AZD1480 suppressed IL-6-induced signaling, migratory prostate cancer cell phenotypes, and metastatic dissemination of prostate cancer in vivo in nude mice. In conclusion, we demonstrate that the cytokine IL-6 directly promotes prostate cancer metastasis in vitro and in vivo via Jak-Stat3 signaling pathway, and that IL-6-driven metastasis can be effectively suppressed by pharmacologic targeting of Jak1/2 using Jak1/2 inhibitor AZD1480. Our results therefore provide a strong rationale for further development of Jak1/2 inhibitors as therapy for metastatic 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.