ArticleOncogene2015
CUX1 modulates polarization of tumor-associated macrophages by antagonizing NF-κB signaling.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- HypoxamiRs in pancreatic cancer: master regulators of the hypoxic tumor microenvironment.Cell biology and toxicology · 2025Review
- Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics.MedComm · 2025Review
- The Homeobox Transcription Factor CUX1 Coordinates Postnatal Epithelial Developmental Timing but Is Dispensable for Lung Organogenesis and Regeneration.American journal of respiratory cell and molecular biology · 2025Article
- An in vivo "turning model" reveals new RanBP9 interactions in lung macrophages.Cell death discovery · 2025Article
- From monocyte-derived macrophages to resident macrophages-how metabolism leads their way in cancer.Molecular oncology · 2024Review
- NF-κB: Governing Macrophages in Cancer.Genes · 2024Review
- Drivers of heterogeneity in synovial fibroblasts in rheumatoid arthritis.Nature immunology · 2023Article
- Role of tumor-associated macrophages in common digestive system malignant tumors.World journal of gastrointestinal oncology · 2023Review
- MX2: Identification and systematic mechanistic analysis of a novel immune-related biomarker for systemic lupus erythematosus.Frontiers in immunology · 2022Article
- Direct Phenotyping and Principal Component Analysis of Type Traits Implicate Novel QTL in Bovine Mastitis through Genome-Wide Association.Animals : an open access journal from MDPI · 2021Article
- CUX1 Facilitates the Development of Oncogenic PropertiesFrontiers in molecular biosciences · 2021Article
- Camptothecin Regulates Microglia Polarization and Exerts Neuroprotective EffectsFrontiers in immunology · 2021Article
- Macrophages in the pancreas: Villains by circumstances, not necessarily by actions.Immunity, inflammation and disease · 2020Review
- Metabolic reprograming of tumor-associated macrophages.Annals of translational medicine · 2020Review
- Depletion of Macrophages Improves Therapeutic Response to Gemcitabine in Murine Pancreas Cancer.Cancers · 2020Article
- CUX1 and IκBζ (NFKBIZ) mediate the synergistic inflammatory response to TNF and IL-17A in stromal fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Bilobalide Alleviated Dextran Sulfate Sodium-Induced Experimental Colitis by Inhibiting M1 Macrophage Polarization Through the NF-κB Signaling Pathway.Frontiers in pharmacology · 2020Article
- CUX1, A Controversial Player in Tumor Development.Frontiers in oncology · 2020Review
- Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma: Origin, Polarization, Function, and Reprogramming.Frontiers in cell and developmental biology · 2020Review
- Upregulated Expression of CUX1 Correlates with Poor Prognosis in Glioma Patients: a Bioinformatic Analysis.Journal of molecular neuroscience : MN · 2019Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many solid cancers including pancreatic ductal adenocarcinoma (PDAC) are characterized by an extensive stromal reaction that is accompanied by infiltrating tumor-associated macrophages (TAMs). The role of TAMs in malignant tumors is only partially understood. Previously, we identified the transcription factor CUX1 as an important mediator of tumor progression in PDAC. Interestingly, we found that CUX1 is highly expressed not only in tumor cells but also in TAMs. On the basis of these data, we aimed to elucidate the effects of CUX1 in TAMs in vitro and in vivo. We analyzed the effects of CUX1 on cytokine expression using overexpression and knockdown strategies. The cytokine regulation by CUX1 was further assessed by reporter assays, DNA pulldown experiments and chromatin-immunoprecipitation. CUX1 expression in TAMs was analyzed in human pancreatic cancer tissues and in a genetic mouse model. Immunohistochemical analysis revealed strong expression levels of CUX1 in a distinct subset of TAMs in human PDAC tissues. Furthermore, its expression increased during tumor progression in a genetic mouse model of PDAC. Profiling experiments showed that CUX1 downregulates several NF-κB-regulated chemokines such as CXCL10, which have been associated with M1 polarization and inhibition of angiogenesis and tumor progression. We could demonstrate that CUX1 interacts with NF-κB p65, leading to reduced binding of NF-κB p65 to the chemokine promoters. In addition, CUX1 reduces acetylation of NF-κB p65 at K310 by recruiting HDAC1. Functionally, CUX1 expression in TAMs antagonizes T-cell attraction and enhances angiogenesis in vitro. We identified CUX1 as an important modulator of the TAMs phenotype and function by modulating NF-κB-dependent cytokines.
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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.