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Available structures
PDBOrtholog search: PDBe RCSB
AliasesCXCL1, FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3, SCYB1, C-X-C motif chemokine ligand 1
External IDsOMIM: 155730; MGI: 1340094; HomoloGene: 136748; GeneCards: CXCL1; OMA:CXCL1 - orthologs
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 4: 73.87 – 73.87 MbChr 5: 91.05 – 91.05 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

The chemokine (C-X-C motif) ligand 1 (CXCL1) is a small peptide belonging to the CXC chemokine family that acts as a chemoattractant for several immune cells, especially neutrophils[5][6] or other non-hematopoietic cells to the site of injury or infection and plays an important role in regulation of immune and inflammatory responses. It was previously called GRO1 oncogene, GROα, neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MGSA-α). CXCL1 was first cloned from a cDNA library of genes induced by platelet-derived growth factor (PDGF) stimulation of BALB/c-3T3 murine embryonic fibroblasts and named "KC" for its location in the nitrocellulose colony hybridization assay.[7] This designation is sometimes erroneously believed to be an acronym and defined as "keratinocytes-derived chemokine". Rat CXCL1 was first reported when NRK-52E (normal rat kidney-52E) cells were stimulated with interleukin-1β (IL-1β) and lipopolysaccharide (LPS) to generate a cytokine that was chemotactic for rat neutrophils, cytokine-induced neutrophil chemoattractant (CINC).[8] In humans, this protein is encoded by the gene CXCL1 [9] and is located on human chromosome 4 among genes for other CXC chemokines.[10]

Structure and expression


CXCL1 exists as both monomer and dimer and both forms are able to bind chemokine receptor CXCR2.[11] However, CXCL1 chemokine is able to dimerize only at higher (micromolar) concentrations and its concentrations are only nanomolar or picomolar upon normal conditions, which means that the form of WT CXCL1 is more likely monomeric while dimeric CXCL1 is present only during infection or injury. CXCL1 monomer consists of three antiparallel β-strands followed by C- terminal α-helix and this α-helix together with the first β-strand are involved in forming a dimeric globular structure.[12]

Upon normal conditions, CXCL1 is not expressed constitutively. It's produced by a variety of immune cells such as macrophages, neutrophils and epithelial cells,[13][14] or Th17 population. Moreover, its expression can be also induced indirectly by IL-1, TNF-α or IL-17 produced again by Th17 cells [15] and is triggered mainly by activation of NF-κB or C/EBPβ signaling pathways predominantly involved in inflammation and leading to production of other inflammatory cytokines.[15]



CXCL1 has a potentially similar role as interleukin-8 (IL-8/CXCL8). After binding to its receptor CXCR2, CXCL1 activates phosphatidylinositol-4,5-bisphosphate 3-kinase-γ (PI3Kγ)/Akt, MAP kinases such as ERK1/ERK2 or phospholipase-β (PLCβ) signaling pathways. CXCL1 is expressed at higher levels during inflammatory responses thus contributing to the process of inflammation.[16] CXCL1 is also involved in the processes of wound healing and tumorigenesis.[17][18][19]

Role in cancer


CXCL1 has a role in angiogenesis and arteriogenesis [20] and thus has been shown to act in the process of tumor progression. The role of CXCL1 was described by several studies in the development of various tumors, such as breast cancer, gastric and colorectal carcinoma or lung cancer.[21][22][23] Also, CXCL1 is secreted by human melanoma cells, has mitogenic properties and is implicated in melanoma pathogenesis.[24][25][26]

Role in nervous system and sensitization


CXCL1 plays a role in spinal cord development by inhibiting the migration of oligodendrocyte precursors.[11] CXCR2 receptor for CXCL1 is expressed in the brain and spinal cord by neurons and oligodendrocytes and during CNS pathologies such as Alzheimer's disease, multiple sclerosis and brain injury also by microglia. An initial study in mice showed evidence that CXCL1 decreased the severity of multiple sclerosis and may offer a neuro-protective function.[27] On the other hand, on the periphery, CXCL1 contributes to the release of prostaglandins and thus causes increased sensitivity to pain and drives nociceptive sensitization via recruitment of neutrophils to the tissue. Phosphorylation of ERK1/ERK2 kinases and activation of NMDA receptors leads to transcription of genes inducing chronic pain, such as c-Fos or cyclooxygenase-2 (COX-2).[16]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163739Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000058427Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Moser B, Clark-Lewis I, Zwahlen R, Baggiolini M (May 1990). "Neutrophil-activating properties of the melanoma growth-stimulatory activity". The Journal of Experimental Medicine. 171 (5): 1797–1802. doi:10.1084/jem.171.5.1797. PMC 2187876. PMID 2185333.
  6. ^ Schumacher C, Clark-Lewis I, Baggiolini M, Moser B (November 1992). "High- and low-affinity binding of GRO alpha and neutrophil-activating peptide 2 to interleukin 8 receptors on human neutrophils". Proceedings of the National Academy of Sciences of the United States of America. 89 (21): 10542–10546. Bibcode:1992PNAS...8910542S. doi:10.1073/pnas.89.21.10542. PMC 50375. PMID 1438244.
  7. ^ Cochran BH, Reffel AC, Stiles CD (July 1983). "Molecular cloning of gene sequences regulated by platelet-derived growth factor". Cell. 33 (3): 939–947. doi:10.1016/0092-8674(83)90037-5. PMID 6872001. S2CID 38719612.
  8. ^ Watanabe K, Kinoshita S, Nakagawa H (June 1989). "Purification and characterization of cytokine-induced neutrophil chemoattractant produced by epithelioid cell line of normal rat kidney (NRK-52E cell)". Biochemical and Biophysical Research Communications. 161 (3): 1093–1099. doi:10.1016/0006-291X(89)91355-7. PMID 2662972.
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  13. ^ Iida N, Grotendorst GR (October 1990). "Cloning and sequencing of a new gro transcript from activated human monocytes: expression in leukocytes and wound tissue". Molecular and Cellular Biology. 10 (10): 5596–5599. doi:10.1128/mcb.10.10.5596. PMC 361282. PMID 2078213.
  14. ^ Becker S, Quay J, Koren HS, Haskill JS (March 1994). "Constitutive and stimulated MCP-1, GRO alpha, beta, and gamma expression in human airway epithelium and bronchoalveolar macrophages". The American Journal of Physiology. 266 (3 Pt 1): L278–L286. doi:10.1152/ajplung.1994.266.3.L278. PMID 8166297.
  15. ^ a b Ma K, Yang L, Shen R, Kong B, Chen W, Liang J, et al. (March 2018). "Th17 cells regulate the production of CXCL1 in breast cancer". International Immunopharmacology. 56: 320–329. doi:10.1016/j.intimp.2018.01.026. PMID 29438938. S2CID 3568978.
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  19. ^ Owen JD, Strieter R, Burdick M, Haghnegahdar H, Nanney L, Shattuck-Brandt R, Richmond A (September 1997). "Enhanced tumor-forming capacity for immortalized melanocytes expressing melanoma growth stimulatory activity/growth-regulated cytokine beta and gamma proteins". International Journal of Cancer. 73 (1): 94–103. doi:10.1002/(SICI)1097-0215(19970926)73:1<94::AID-IJC15>3.0.CO;2-5. PMID 9334815.
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  24. ^ Anisowicz A, Bardwell L, Sager R (October 1987). "Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells". Proceedings of the National Academy of Sciences of the United States of America. 84 (20): 7188–7192. Bibcode:1987PNAS...84.7188A. doi:10.1073/pnas.84.20.7188. PMC 299255. PMID 2890161.
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