ArticleProceedings of the National Academy of Sciences of the United States of America2011
Monomeric and dimeric CXCL12 inhibit metastasis through distinct CXCR4 interactions and signaling pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 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
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Who cites it
129 citing papers in PubMed, 206 citations in OpenAlex.
- CXCR4, CXCL12 and the relative CXCL12-CXCR4 expression as prognostic factors in colon cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Trial
- Biosafety assessment of engineered CCL20 locked dimers in vivo.Cell biology and toxicology · 2025Article
- CXCR4 mediated recognition of HIV envelope spike and inhibition by CXCL12.Nature communications · 2025Article
- CXCL12 chemokine dimer signaling modulates acute myelogenous leukemia cell migration through altered receptor internalization.Scientific reports · 2025Article
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
- Article
- Perforated Calculous Cholecystitis and Incidental Squamous Cell Carcinoma of the Gallbladder-A Complex Relationship with a Difficult Management in the Acute Setting.Medicina (Kaunas, Lithuania) · 2025Article
- Structural insights into CXCR4 modulation and oligomerization.Nature structural & molecular biology · 2025Article
- CXCL12 restricts tumor growth by suppressing the Ras, ERK1/2, c-Myc, and the immune checkpoint PD-L1 pathways.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- MACC1 revisited - an in-depth review of a master of metastasis.Biomarker research · 2024Review
- Atypical chemokine receptors in the immune system.Nature reviews. Immunology · 2024Review
- Review
- CXCL14 as a Key Regulator of Neuronal Development: Insights from Its Receptor and Multi-Omics Analysis.International journal of molecular sciences · 2024Article
- Monomeric CXCL12-Engineered Adipose-Derived Stem Cells Transplantation for the Treatment of Ischemic Stroke.International journal of molecular sciences · 2024Article
- Unraveling impact and potential mechanisms of baseline pain on efficacy of immunotherapy in lung cancer patients: a retrospective and bioinformatic analysis.Frontiers in immunology · 2024Article
- Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.International journal of molecular sciences · 2023Review
- The Chemokine, CCL20, and Its Receptor, CCR6, in the Pathogenesis and Treatment of Psoriasis and Psoriatic Arthritis.Journal of psoriasis and psoriatic arthritis · 2023Review
- Chemokine Heteromers and Their Impact on Cellular Function-A Conceptual Framework.International journal of molecular sciences · 2023Review
- Multiple mechanisms of self-association of chemokine receptors CXCR4 and CCR5 demonstrated by deep mutagenesis.bioRxiv : the preprint server for biology · 2023Article
- New pairings and deorphanization among the atypical chemokine receptor family - physiological and clinical relevance.Frontiers in immunology · 2023Review
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Chemokines and chemokine receptors are extensively and broadly involved in cancer metastasis. Previously, we demonstrated that epigenetic silencing of the chemokine CXCL12 sensitizes breast and colon cancer cells to endocrine signaling and metastasis to distant tissues. Yet, the precise mechanism whereby CXCL12 production by tumor cells regulates dissemination remains unclear. Here, we show that administration of CXCL12 extended survival of tumor-bearing mice by potently limiting metastasis of colorectal carcinoma or murine melanoma. Because secreted CXCL12 is a mixture of monomeric and dimeric species in equilibrium, oligomeric variants that either promote (monomer) or halt (dimer) chemotaxis were used to dissect the mechanisms interrupting carcinoma metastasis. Monomeric CXCL12 mobilized intracellular calcium, inhibited cAMP signaling, recruited β-arrestin-2, and stimulated filamentous-actin accumulation and cell migration. Dimeric CXCL12 activated G-protein-dependent calcium flux, adenylyl cyclase inhibition, and the rapid activation of ERK1/2, but only weakly, if at all, recruited arrestin, stimulated actin polymerization, or promoted chemotaxis. NMR analyses illustrated that CXCL12 monomers made specific contacts with CXCR4 that were lost following dimerization. Our results establish the potential for inhibiting CXCR4-mediated metastasis by administration of CXCL12. Chemokine-mediated migration and β-arrestin responses did not dictate the antitumor effect of CXCL12. We conclude that cellular migration is tightly regulated by selective CXCR4 signaling evoked by unique interactions with distinct ligand quaternary structures.
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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.