ArticleThe Journal of biological chemistry2014
Proteasome inhibition increases recruitment of IκB kinase β (IKKβ), S536P-p65, and transcription factor EGR1 to interleukin-8 (IL-8) promoter, resulting in increased IL-8 production in ovarian cancer cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 65 citations in OpenAlex.
- A novel function of STARD7: its tumor-promoting role involves the activation of NF-κB signaling pathway in ovarian cancer.Human cell · 2025Article
- Hypoxia-induced EGR1 remodels neutrophils to suppress antitumor immunity.Science immunology · 2025Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- The CXCL8-CXCR2 axis promotes M2 macrophage polarization in ovarian cancer via RASGRP4-mediated mTOR-STAT3 signaling.Apoptosis : an international journal on programmed cell death · 2025Article
- IFNγ-Induced Bcl3, PD-L1 and IL-8 Signaling in Ovarian Cancer: Mechanisms and Clinical Significance.Cancers · 2024Review
- The Role of Cytokines in Activation of Tumour-promoting Pathways and Emergence of Cancer Drug Resistance.Current topics in medicinal chemistry · 2024Review
- Mechanisms underlying reversed TRAIL sensitivity in acquired bortezomib-resistant non-small cell lung cancer cells.Cancer drug resistance (Alhambra, Calif.) · 2024Article
- Article
- Human Red Blood Cells Modulate Cytokine Expression in Monocytes/Macrophages Under Anoxic Conditions.Frontiers in physiology · 2021Article
- Activated heme synthesis regulates glycolysis and oxidative metabolism in breast and ovarian cancer cells.PloS one · 2021Article
- The structure and regulation of the E3 ubiquitin ligase HUWE1 and its biological functions in cancer.Investigational new drugs · 2020Review
- Non-lethal proteasome inhibition activates pro-tumorigenic pathways in multiple myeloma cells.Journal of cellular and molecular medicine · 2019Article
- EGR1 regulates angiogenic and osteoclastogenic factors in prostate cancer and promotes metastasis.Oncogene · 2019Article
- Predicting Postoperative Liver Dysfunction Based on Blood-Derived MicroRNA Signatures.Hepatology (Baltimore, Md.) · 2019Article
- IKKβ targeting reduces KRAS-induced lung cancer angiogenesis in vitro and in vivo: A potential anti-angiogenic therapeutic target.Lung cancer (Amsterdam, Netherlands) · 2019Article
- Regulation of Chemokines and Cytokines by Histone Deacetylases and an Update on Histone Decetylase Inhibitors in Human Diseases.International journal of molecular sciences · 2019Review
- Combination Therapies Targeting HDAC and IKK in Solid Tumors.Trends in pharmacological sciences · 2018Review
- Article
- GRO-α and IL-8 enhance ovarian cancer metastatic potential via the CXCR2-mediated TAK1/NFκB signaling cascade.Theranostics · 2018Article
- Underlying Causes and Therapeutic Targeting of the Inflammatory Tumor Microenvironment.Frontiers in cell and developmental biology · 2018Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Proinflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8) contributes to ovarian cancer progression through its induction of tumor cell proliferation, survival, angiogenesis, and metastasis. Proteasome inhibition by bortezomib, which has been used as a frontline therapy in multiple myeloma, has shown only limited effectiveness in ovarian cancer and other solid tumors. However, the responsible mechanisms remain elusive. Here, we show that proteasome inhibition dramatically increases the IL-8 expression and release in ovarian cancer cells. The responsible mechanism involves an increased nuclear accumulation of IκB kinase β (IKKβ) and an increased recruitment of the nuclear IKKβ, p65-phosphorylated at Ser-536, and the transcription factor early growth response-1 (EGR-1) to the endogenous IL-8 promoter. Coimmunoprecipitation studies identified the nuclear EGR-1 associated with IKKβ and with p65, with preferential binding to S536P-p65. Both IKKβ activity and EGR-1 expression are required for the increased IL-8 expression induced by proteasome inhibition in ovarian cancer cells. Interestingly, in multiple myeloma cells the IL-8 release is not increased by bortezomib. Together, these data indicate that the increased IL-8 release may represent one of the underlying mechanisms responsible for the decreased effectiveness of proteasome inhibition in ovarian cancer treatment and identify IKKβ and EGR-1 as potential new targets in ovarian cancer combination therapies.
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