ArticleThe Journal of biological chemistry2012
CCL2/CCR2 chemokine signaling coordinates survival and motility of breast cancer cells through Smad3 protein- and p42/44 mitogen-activated protein kinase (MAPK)-dependent mechanisms.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 1 of them a synthesis that pooled it.
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Who cites it
130 citing papers in PubMed, 1 synthesis or guideline pooled it, 201 citations in OpenAlex.
- Monocyte chemotactic protein-1 expression as a prognosic biomarker in patients with solid tumor: a meta analysis.International journal of clinical and experimental pathology · 2014Pooled it
- Trial
- Obesity-driven adipokine signaling in breast cancer: mechanistic insights, therapeutic challenges, and opportunities for precision oncology.Journal of pathology and translational medicine · 2026Article
- Chemokine-chemokine receptor axis: Emerging immunotherapeutic paradigms for solid tumor microenvironment reprogramming.Chinese medical journal · 2026Review
- Native chromatome profiling reveals hundreds of metabolic enzymes in the nucleus across tissues.Nature communications · 2026Article
- CCL2/CCR2 signaling pathway in tumorigenesis and metastasis (Review).Oncology letters · 2025Review
- Cooperative CCL2/CCR2 and HGF/MET signaling enhances breast cancer growth and invasion associated with metabolic reprogramming.Cancer biology & therapy · 2025Article
- Chimeric diphtheria toxin-CCL8 cytotoxic peptide for breast cancer management.Molecular oncology · 2025Article
- MCP-1-CCR2-M2 macrophages axis contributes to diffuse large B-cell lymphoma progression and inhibits antitumor immune response.Scientific reports · 2025Article
- Epithelial Regnase-1 inhibits colorectal tumor growth by regulating IL-17 signaling via degradation ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- CCL2 blockade combined with PD-1/P-selectin immunomodulators impedes breast cancer brain metastasis.Brain : a journal of neurology · 2025Article
- The power of many: Multilevel targeting of representative chemokine and metabolite GPCRs in personalized cancer therapy.European journal of immunology · 2024Review
- A machine learning model revealed that exosome small RNAs may participate in the development of breast cancer through the chemokine signaling pathway.BMC cancer · 2024Article
- CCL2 signaling promotes skeletal muscle wasting in non-tumor and breast tumor models.Disease models & mechanisms · 2024Article
- Targeting CCL2-CCR2 signaling pathway alleviates macrophage dysfunction in COPD via PI3K-AKT axis.Cell communication and signaling : CCS · 2024Article
- Dissecting the MUC5AC/ANXA2 signaling axis: implications for brain metastasis in lung adenocarcinoma.Experimental & molecular medicine · 2024Article
- MLL1 regulates cytokine-driven cell migration and metastasis.Science advances · 2024Article
- Dual effect of vitamin DBMC cancer · 2024Article
- How chemokines organize the tumour microenvironment.Nature reviews. Cancer · 2024Review
- Regulation of regulatory T cells and tumor-associated macrophages in gastric cancer tumor microenvironment.Cancer medicine · 2024Review
70 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Increased cell motility and survival are important hallmarks of metastatic tumor cells. However, the mechanisms that regulate the interplay between these cellular processes remain poorly understood. In these studies, we demonstrate that CCL2, a chemokine well known for regulating immune cell migration, plays an important role in signaling to breast cancer cells. We report that in a panel of mouse and human breast cancer cell lines CCL2 enhanced cell migration and survival associated with increased phosphorylation of Smad3 and p42/44MAPK proteins. The G protein-coupled receptor CCR2 was found to be elevated in breast cancers, correlating with CCL2 expression. RNA interference of CCR2 expression in breast cancer cells significantly inhibited CCL2-induced migration, survival, and phosphorylation of Smad3 and p42/44MAPK proteins. Disruption of Smad3 expression in mammary carcinoma cells blocked CCL2-induced cell survival and migration and partially reduced p42/44MAPK phosphorylation. Ablation of MAPK phosphorylation in Smad3-deficient cells with the MEK inhibitor U0126 further reduced cell survival but not migration. These data indicate that Smad3 signaling through MEK-p42/44MAPK regulates CCL2-induced cell motility and survival, whereas CCL2 induction of MEK-p42/44MAPK signaling independent of Smad3 functions as an alternative mechanism for cell survival. Furthermore, we show that CCL2-induced Smad3 signaling through MEK-p42/44MAPK regulates expression and activity of Rho GTPase to mediate CCL2-induced breast cancer cell motility and survival. With these studies, we characterize an important role for CCL2/CCR2 chemokine signaling in regulating the intrinsic relationships between breast cancer cell motility and survival with implications on the metastatic process.
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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.