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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CXCL3
C-X-C motif chemokine ligand 3
Chromosome 4 · 4q13.3
NCBI Gene: 2921Ensembl: ENSG00000163734.4HGNC: HGNC:4604UniProt: P19876
68PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GO:0005615chemokine activityneutrophil chemotaxisextracellular regionneurodegenerative diseaseneoplasmcolorectal carcinomaattention deficit hyperactivity disorder
✦AI Summary

CXCL3 is a C-X-C chemokine that functions primarily as a neutrophil chemoattractant through CXCR2 receptor binding 1. The processed form GRO-gamma(5-73) exhibits enhanced chemotactic activity for neutrophilic granulocytes, and CXCL3 exerts effects on endothelial cells in autocrine fashion. Mechanistically, CXCL3 expression is regulated by multiple pathways: the JAK2/STAT3 pathway in colorectal cancer 2, the KRAS-IRF2 axis in colorectal cancer 3, NKX2-1 suppression in lung adenocarcinoma 4, and PDGF receptor signaling in gastric cancer 5. CXCL3 recruits myeloid-derived suppressor cells (MDSCs) and neutrophils to tumor microenvironments via CXCR2 signaling. In disease contexts, elevated CXCL3 correlates with poor prognosis in pancreatic cancer 6 and colorectal cancer 2. CXCL3 promotes cancer progression through multiple mechanisms: orchestrating neutrophil extracellular traps in aortic dissection 1, facilitating pancreatic cancer metastasis through myofibroblast transition 6, accumulating immunosuppressive PMN-MDSCs in colorectal cancer 2, and inducing ferroptotic neutrophils that suppress antitumor immunity in breast cancer 7. In rheumatoid arthritis, CXCL3 is upregulated in synovial macrophages via NF-κB signaling 8. Clinically, CXCR2 antagonism or CXCL3 blockade restores anti-PD-1 immunotherapy responsiveness and reduces tumor progression across multiple cancer types.

Sources cited
1
CXCL3 is a C-X-C chemokine that functions primarily as a neutrophil chemoattractant through CXCR2 receptor binding .
PMID: 39737994
2
Mechanistically, CXCL3 expression is regulated by multiple pathways: the JAK2/STAT3 pathway in colorectal cancer , the KRAS-IRF2 axis in colorectal cancer , NKX2-1 suppression in lung adenocarcinoma , and PDGF receptor signaling in gastric cancer .
PMID: 40179015
3
Mechanistically, CXCL3 expression is regulated by multiple pathways: the JAK2/STAT3 pathway in colorectal cancer , the KRAS-IRF2 axis in colorectal cancer , NKX2-1 suppression in lung adenocarcinoma , and PDGF receptor signaling in gastric cancer .
PMID: 30905761
4
Mechanistically, CXCL3 expression is regulated by multiple pathways: the JAK2/STAT3 pathway in colorectal cancer , the KRAS-IRF2 axis in colorectal cancer , NKX2-1 suppression in lung adenocarcinoma , and PDGF receptor signaling in gastric cancer .
PMID: 39113226
5
Mechanistically, CXCL3 expression is regulated by multiple pathways: the JAK2/STAT3 pathway in colorectal cancer , the KRAS-IRF2 axis in colorectal cancer , NKX2-1 suppression in lung adenocarcinoma , and PDGF receptor signaling in gastric cancer .
PMID: 36543251
6
In disease contexts, elevated CXCL3 correlates with poor prognosis in pancreatic cancer and colorectal cancer .
PMID: 33568427
7
CXCL3 promotes cancer progression through multiple mechanisms: orchestrating neutrophil extracellular traps in aortic dissection , facilitating pancreatic cancer metastasis through myofibroblast transition , accumulating immunosuppressive PMN-MDSCs in colorectal cancer , and inducing ferroptotic neutrophils that suppress antitumor immunity in breast cancer .
PMID: 39531510
8
In rheumatoid arthritis, CXCL3 is upregulated in synovial macrophages via NF-κB signaling .
PMID: 36940312
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.26Weak
neoplasmOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.10Suggestive
attention deficit hyperactivity disorderOpen Targets
0.09Suggestive
Mobius syndromeOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
breast carcinomaOpen Targets
0.08Suggestive
head and neck squamous cell carcinomaOpen Targets
0.08Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.08Suggestive
colitisOpen Targets
0.08Suggestive
liver cancerOpen Targets
0.07Suggestive
attention deficit-hyperactivity disorder 8Open Targets
0.07Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.07Suggestive
intellectual disability, autosomal recessive 59Open Targets
0.07Suggestive
movement disorderOpen Targets
0.07Suggestive
schizophrenia 15Open Targets
0.07Suggestive
preeclampsiaOpen Targets
0.05Suggestive
ulcerative colitisOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CX3CR1Protein interaction100%CCR2Protein interaction100%CXCL14Protein interaction100%CXCR4Protein interaction100%CXCR1Protein interaction99%CCL11Protein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
51%
Liver
6%
Heart
3%
Ovary
2%
Brain
0%
Gene Interaction Network
Click a node to explore
CXCL3CX3CR1CCR2CXCL14CXCR4CXCR1CCL11
PROTEIN STRUCTURE
Preparing viewer…
PDB8XX3 · 3.38 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.38LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.82 [0.50–1.38]
RankingsWhere CXCL3 stands among ~20K protein-coding genes
  • #6,893of 20,598
    Most Researched68
  • #14,390of 17,882
    Most Constrained (LOEUF)1.38
Genes detectedCXCL3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Integrated multi-omics profiling reveals neutrophil extracellular traps potentiate Aortic dissection progression.
PMID: 39737994
Nat Commun · 2024
1.00
2
Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism.
PMID: 33568427
Gut · 2022
0.90
3
Gut microbial metabolite 4-hydroxybenzeneacetic acid drives colorectal cancer progression via accumulation of immunosuppressive PMN-MDSCs.
PMID: 40179015
J Clin Invest · 2025
0.80
4
Ferroptotic Neutrophils Induce Immunosuppression and Chemoresistance in Breast Cancer.
PMID: 39531510
Cancer Res · 2025
0.70
5
KRAS-IRF2 Axis Drives Immune Suppression and Immune Therapy Resistance in Colorectal Cancer.
PMID: 30905761
Cancer Cell · 2019
0.60