ArticleNeoplasia (New York, N.Y.)2015
Smac Mimetic-Induced Upregulation of CCL2/MCP-1 Triggers Migration and Invasion of Glioblastoma Cells and Influences the Tumor Microenvironment in a Paracrine Manner.
Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
24 citing papers in PubMed, 42 citations in OpenAlex.
- Cell death in glioblastoma and the central nervous system.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Chemokine ligand 2: beyond chemotaxis-a multifaceted role in tumor progression.Frontiers in immunology · 2025Review
- The Mechanism of Action of Exosomes Derived from Glioblastoma Cells.Current medicinal chemistry · 2025Review
- Article
- Influence of GO-Antisense miRNA-21 on the Expression of Selected Cytokines at Glioblastoma Cell Lines.International journal of nanomedicine · 2023Article
- Perivascular Stromal Cells Instruct Glioblastoma Invasion, Proliferation, and Therapeutic Response within an Engineered Brain Perivascular Niche Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- The Dynamics of Tumor-Infiltrating Myeloid Cell Activation and the Cytokine Expression Profile in a Glioma Resection Site during the Post-Surgical Period in Mice.Brain sciences · 2022Article
- Palmitoyl transferases act as potential regulators of tumor-infiltrating immune cells and glioma progression.Molecular therapy. Nucleic acids · 2022Article
- Multifaceted microglia - key players in primary brain tumour heterogeneity.Nature reviews. Neurology · 2021Review
- IL-1β promotes cervical cancer through activating NF-κB/CCL-2.International journal of clinical and experimental pathology · 2021Article
- OTUD7B suppresses Smac mimetic-induced lung cancer cell invasion and migration via deubiquitinating TRAF3.Journal of experimental & clinical cancer research : CR · 2020Article
- The anti-inflammatory drug dimethyl itaconate protects against colitis-associated colorectal cancer.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Ethanol Extract of Lycopodium serratum Thunb. Attenuates Lipopolysaccharide-Induced C6 Glioma Cells Migration via Matrix Metalloproteinase-9 Expression.Chinese journal of integrative medicine · 2018Article
- Identification of radiation responsive genes and transcriptome profiling via complete RNA sequencing in a stable radioresistant U87 glioblastoma model.Oncotarget · 2018Article
- Targeted nanocomplex carrying siRNA against MALAT1 sensitizes glioblastoma to temozolomide.Nucleic acids research · 2018Article
- Cell death-based treatment of glioblastoma.Cell death & disease · 2018Review
- Glioblastoma and acute myeloid leukemia: malignancies with striking similarities.Journal of neuro-oncology · 2018Review
- Impact of mesenchymal stem cells' secretome on glioblastoma pathophysiology.Journal of translational medicine · 2017Article
- Effect of glucose level on chemical hypoxia- and hydrogen peroxide-induced chemokine expression in human glioblastoma cell lines.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
- NCTD promotes Birinapant-mediated anticancer activity in breast cancer cells by downregulation of c-FLIP.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Second mitochondria-derived activator of caspase (Smac) mimetics are considered as promising anticancer therapeutics that are currently under investigation in early clinical trials. They induce apoptosis by antagonizing inhibitor of apoptosis proteins, which are frequently overexpressed in cancer. We previously reported that Smac mimetics, such as BV6, additionally exert non-apoptotic functions in glioblastoma (GBM) cells by stimulating migration and invasion in a nuclear factor kappa B (NF-κB)-dependent manner. Because NF-κB target genes mediating these effects are largely unknown, we performed whole-genome expression analyses. Here, we identify chemokine (C-C motif) ligand 2 (CCL2) as the top-listed NF-κB-regulated gene being upregulated upon BV6 treatment in GBM cells. BV6-induced upregulation and secretion of CCL2 are required for migration and invasion of GBM cells because knockdown of CCL2 in GBM cells abolishes these effects. Co-culture experiments of GBM cells with non-malignant astroglial cells reveal that BV6-stimulated secretion of CCL2 by GBM cells into the supernatant triggers migration of astroglial cells toward GBM cells because CCL2 knockdown in BV6-treated GBM cells impedes BV6-stimulated migration of astroglial cells. In conclusion, we identify CCL2 as a BV6-induced NF-κB target gene that triggers migration and invasion of GBM cells and exerts paracrine effects on the GBM's microenvironment by stimulating migration of astroglial cells. These findings provide novel insights into the biological functions of Smac mimetics with important implications for the development of Smac mimetics as cancer therapeutics.
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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.