ArticleJournal of cellular biochemistry2012
IL-4 induces proliferation in prostate cancer PC3 cells under nutrient-depletion stress through the activation of the JNK-pathway and survivin up-regulation.
Article in Journal of cellular biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 74 citations in OpenAlex.
- Restoration of Immune Surveillance in Prostate Cancer Prevention by Sulforaphane in Hi-Myc Mice.Molecular carcinogenesis · 2026Article
- Tumor Microenvironment Onmyoji: Cytokines with Dual Protumor and Antitumor Roles.Cancer communications (London, England) · 2026Review
- Integrating GEO, network pharmacology, and in vitro assays to explore the pharmacological mechanism of Bruceae Fructus against laryngeal cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- The role of proinflammatory cytokines and CXC chemokines (CXCL1-CXCL16) in the progression of prostate cancer: insights on their therapeutic management.Cellular & molecular biology letters · 2024Review
- Arming CAR-T cells with cytokines and more: Innovations in the fourth-generation CAR-T development.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Review
- Evidence of a role for interleukin-6 in anoikis resistance in oral squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2022Article
- Tumor promoting roles of IL-10, TGF-β, IL-4, and IL-35: Its implications in cancer immunotherapy.SAGE open medicine · 2022Review
- JNK in Tumor Microenvironment: Present Findings and Challenges in Clinical Translation.Cancers · 2021Review
- Enhancing CAR-T cell efficacy in solid tumors by targeting the tumor microenvironment.Cellular & molecular immunology · 2021Review
- Involvement of IL-4, IL-13 and Their Receptors in Pancreatic Cancer.International journal of molecular sciences · 2021Review
- A Double-Edged Sword Role of Cytokines in Prostate Cancer Immunotherapy.Frontiers in oncology · 2021Review
- Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system.Frontiers of medicine · 2020Review
- Antioxidant or pro-oxidant and glutathione transferase P1-1 inhibiting activities for Tamarindus indica seeds and their cytotoxic effect on MCF-7 cancer cell line.Journal, genetic engineering & biotechnology · 2020Article
- Dioscin elicits anti-tumour immunity by inhibiting macrophage M2 polarization via JNK and STAT3 pathways in lung cancer.Journal of cellular and molecular medicine · 2020Article
- Interleukin-4 Signaling Plays a Major Role in Urogenital Schistosomiasis-Associated Bladder Pathogenesis.Infection and immunity · 2020Article
- Jumonji domain-containing protein 6 protein and its role in cancer.Cell proliferation · 2020Review
- ERK is a Pivotal Player of Chemo-Immune-Resistance in Cancer.International journal of molecular sciences · 2019Review
- The Role Of Hepatic Stellate Cells In Promoting Liver Metastasis Of Colorectal Carcinoma.OncoTargets and therapy · 2019Article
- Metastatic prostate cancer remains incurable, why?Asian journal of urology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin (IL)-4 plays a critical role in the regulation of immune responses and has been detected at high levels in the tumor microenvironment of cancer patients where it correlates with the grade of malignancy. The direct effect of IL-4 on cancer cells has been associated with increased cell survival; however, its role in cancer cell proliferation and related mechanisms is still unclear. Here it was shown that in a nutrient-depleted environment, IL-4 induces proliferation in prostate cancer PC3 cells. In these cells, under nutrient-depletion stress, IL-4 activates mitogen-activated protein kinases (MAPKs), including Erk, p38, and JNK. Using MAP-signaling-specific inhibitors, it was shown that IL-4-induced proliferation is mediated by JNK activation. In fact, JNK-inhibitor-V (JNKi-V) stunted IL-4-mediated cell proliferation. Furthermore, it was found that IL-4 induces survivin up-regulation in nutrient-depleted cancer cells. Using survivin-short-hairpin-RNAs (shRNAs), it was demonstrated that in this milieu survivin expression above a threshold limit is critical to the mechanism of IL-4-mediated proliferation. In addition, the significance of survivin up-regulation in a stressed environment was assessed in prostate cancer mouse xenografts. It was found that survivin knockdown decreases tumor progression in correlation with cancer cell proliferation. Furthermore, under nutrient depletion stress, IL -4 could induce proliferation in cancer cells from multiple origins: MDA-MB-231 (breast), A253 (head and neck), and SKOV-3 (ovarian). Overall, these findings suggest that in a tumor microenvironment under stress conditions, IL-4 triggers a simultaneous activation of the JNK-pathway and the up-regulation of survivin turning on a cancer proliferation mechanism.
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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.