ArticleExperimental & molecular medicine2017
NF-κB signaling regulates cell-autonomous regulation of CXCL10 in breast cancer 4T1 cells.
Article in Experimental & molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Pooled it
- Fibroblast STAT3 Activation Drives Organ-Specific Premetastatic Niche Formation.Cancer research · 2026Article
- Advances in intratumoral immunotherapy from a neuro-immune-endocrine perspective for breast cancer treatment.Frontiers in oncology · 2026Review
- TAB2 controls a TAK1-independent cell death checkpoint at the level of TNFR1 complex II in the TNF pathway.Cell death and differentiation · 2026Article
- Particle Shape Modulates the Function of Adoptive Macrophage Transfers.Advanced healthcare materials · 2025Article
- The CXCL10-CXCR3 Axis Induces Tumor-Associated Neutrophils to Interfere with CTLs-Mediated Antitumor Activity in EBV-Associated Epithelial Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of CXC chemokines and receptors in breast cancer.Clinical and experimental medicine · 2025Review
- NLRP4 unlocks an NK/macrophages-centered ecosystem to suppress non-small cell lung cancer.Biomarker research · 2025Article
- Role of CXCL10 released from osteocytes in response to TNF-α stimulation on osteoclasts.Scientific reports · 2025Article
- Piezo1 promotes vibration-induced vascular smooth muscle injury by regulating the NF-κB/p65 axis.Communications biology · 2025Article
- Hybridization Design and High-Throughput Screening of Peptides with Immunomodulatory and Antioxidant Activities.International journal of molecular sciences · 2025Article
- CXCR3 inhibitors for therapeutic interventions: current status and perspectives.Frontiers in pharmacology · 2025Review
- Herpes simplex virus spreads rapidly in human foreskin, partly driven by chemokine-induced redistribution of Nectin-1 on keratinocytes.PLoS pathogens · 2024Article
- A review of the pleiotropic actions of the IFN-inducible CXC chemokine receptor 3 ligands in the synovial microenvironment.Cellular and molecular life sciences : CMLS · 2023Review
- Article
- Chemokines network in bone metastasis: Vital regulators of seeding and soiling.Seminars in cancer biology · 2022Review
- Article
- Review
- CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity.Nature communications · 2022Article
- Systemic CXCL10 is a predictive biomarker of vitiligo lesional skin infiltration, PUVA, NB-UVB and corticosteroid treatment response and outcome.Archives of dermatological research · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibited basal and CXCL10-induced CXCL10 expression and cell motility in 4T1 cells. Treatment of 4T1 cells with CXCL10 increased the expression of P65, a subunit of the NF-κB pathway, via activation of the NF-κB transcriptional activity. Ectopic overexpression of P65 increased CXCL10 secretion and blunted JN-2-induced suppression of CXCL10 secretion, whereas overexpression of IκBα suppressed CXCL10 secretion. These results indicate that the CXCL10/CXCR3 axis creates a positive feedback loop through the canonical NF-κB signaling pathway in 4T1 cells. In addition, treatment of osteoblasts with conditioned medium from JN-2-treated 4T1 cells inhibited the expression of RANKL, a crucial cytokine for osteoclast differentiation, which resulted in an inhibitory effect on osteoclast differentiation in the co-culture system of bone marrow-derived macrophages and osteoblasts. Direct intrafemoral injection of 4T1 cells induced severe bone destruction; however, this effect was suppressed by the CXCR3 antagonist via downregulation of P65 expression in an animal model. Collectively, these results suggest that the CXCL10/CXCR3-mediated NF-κB signaling pathway plays a role in the control of autonomous regulation of CXCL10 and malignant tumor properties in breast cancer 4T1 cells.
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