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Gene Review

CXCL1  -  chemokine (C-X-C motif) ligand 1 (melanoma...

Homo sapiens

Synonyms: C-X-C motif chemokine 1, FSP, GRO, GRO-alpha(1-73), GRO1, ...
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Disease relevance of CXCL1


Psychiatry related information on CXCL1


High impact information on CXCL1

  • Third, both MGSA and IL-8 blocked the binding of the parasite ligand and the invasion of human erythrocytes by P. knowlesi, suggesting the possibility of receptor blockade for anti-malarial therapy [7].
  • Like NAP-2 and GRO alpha, ENA-78 stimulates neutrophils, inducing chemotaxis, a rise in intracellular free calcium and exocytosis [8].
  • NAP-3 (MGSA/gro) appears to represent the first member of the novel supergene family of beta-thromboglobulin-like host defense cytokines, which expresses both mitogenic as well as proinflammatory properties at the nanogram level [9].
  • Determination of neutrophil chemotactic activity of NAP-3 revealed a typical bell-shaped dose-response curve (ED50 = 2 ng/ml) with no significant neutrophil chemotactic activity at doses greater than 200 ng/ml [9].
  • The sequence is identical to that found for the 13-kD moiety of melanoma growth stimulating activity (MGSA) and the product of the oncogene gro [9].

Chemical compound and disease context of CXCL1


Biological context of CXCL1


Anatomical context of CXCL1

  • The chemokines, CXC ligand 1 (CXCL1) and CXCL8, but not CXCL5, are highly expressed in most of the melanoma cell lines, suggesting that the constitutive production of chemokines is highly correlated to endogenous NF-kappaB activity [18].
  • In addition, the melanoma growth and migration stimulatory chemokines CXCL1 and CXCL2 were significantly up-regulated in the cocultured fibroblasts [19].
  • IL-8/CXCL8 and growth-related oncogene alpha/CXCL1 induce chondrocyte hypertrophic differentiation [20].
  • We identified two chemokines: Growth-Regulated Oncogene-alpha (Gro-alpha; CXCL1) and Regulated on Activation Normal T Cell-Expressed and Secreted (RANTES; CCL5), to be secreted by several human tumor cell lines [21].
  • At the functional level, following stimulation with the proinflammatory cytokine, interleukin-1beta (IL-1beta), we found high-level synthesis of CXCL1 by human fetal astrocytes in vitro [4].

Associations of CXCL1 with chemical compounds


Physical interactions of CXCL1

  • 125I-MGSA binding was specific and could not be displaced by unlabeled IL-8 [27].
  • We show here that the CXCL1 maximal binding to CXCR2 expressed on HEK293 and CHO-K1 cells is dependent on the presence of cell surface HSPGs [22].
  • Scatchard analysis of MGSA binding showed that the chemokine receptor from renal tissues had a binding affinity of 3.5 nM similar to that observed for the erythroid isoform (5-10 nM) [28].
  • Receptor binding and biological studies with the alanine scan mutants of MGSA demonstrate that MGSA binds to DARC and the IL-8RB through distinct binding regions [10].

Regulatory relationships of CXCL1


Other interactions of CXCL1

  • The chemotactic response to the CXC and CC chemokines correlated with the receptor expression except that all 3 populations responded to GRO-alpha, despite their lack of CXCR2 expression [32].
  • Chemokine levels in human liver homogenates: associations between GRO alpha and histopathological evidence of alcoholic hepatitis [33].
  • Three of the 10 transcripts encoded CXC chemokines (CXCL1, CXCL2, and CXCL6) [34].
  • ZR-75-1 responded to MIP-1beta and GRO-alpha, giving maximum migration indices of 3.7 and 5.3, respectively, and exhibited a migratory response to MIP-1alpha, IL-8 and MCP-1 although to a lower degree [35].
  • Furthermore, IL-8 induced a significant increase in extracellular signal-regulated kinase 2 phosphorylation, whereas MGSA/GROalpha was much less effective [36].

Analytical, diagnostic and therapeutic context of CXCL1


  1. Induction of melanoma in murine macrophage inflammatory protein 2 transgenic mice heterozygous for inhibitor of kinase/alternate reading frame. Yang, J., Luan, J., Yu, Y., Li, C., DePinho, R.A., Chin, L., Richmond, A. Cancer Res. (2001) [Pubmed]
  2. Expression of angiogenic factors vascular endothelial growth factor and interleukin-8/CXCL8 is highly responsive to ambient glutamine availability: role of nuclear factor-kappaB and activating protein-1. Bobrovnikova-Marjon, E.V., Marjon, P.L., Barbash, O., Vander Jagt, D.L., Abcouwer, S.F. Cancer Res. (2004) [Pubmed]
  3. CXC chemokine receptor-2 ligands are required for neutrophil-mediated host defense in experimental brain abscesses. Kielian, T., Barry, B., Hickey, W.F. J. Immunol. (2001) [Pubmed]
  4. Role for CXCR2 and CXCL1 on glia in multiple sclerosis. Omari, K.M., John, G., Lango, R., Raine, C.S. Glia (2006) [Pubmed]
  5. Chemotactic activity of CXCL5 in cerebrospinal fluid of children with bacterial meningitis. Zwijnenburg, P.J., de Bie, H.M., Roord, J.J., van der Poll, T., van Furth, A.M. J. Neuroimmunol. (2003) [Pubmed]
  6. Association study of the chemokine, CXC motif, ligand 1 (CXCL1) gene with sporadic Alzheimer's disease in a Japanese population. Tamura, Y., Sakasegawa, Y., Omi, K., Kishida, H., Asada, T., Kimura, H., Tokunaga, K., Hachiya, N.S., Kaneko, K., Hohjoh, H. Neurosci. Lett. (2005) [Pubmed]
  7. A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. Horuk, R., Chitnis, C.E., Darbonne, W.C., Colby, T.J., Rybicki, A., Hadley, T.J., Miller, L.H. Science (1993) [Pubmed]
  8. Structure and neutrophil-activating properties of a novel inflammatory peptide (ENA-78) with homology to interleukin 8. Walz, A., Burgener, R., Car, B., Baggiolini, M., Kunkel, S.L., Strieter, R.M. J. Exp. Med. (1991) [Pubmed]
  9. Lipopolysaccharide-stimulated human monocytes secrete, apart from neutrophil-activating peptide 1/interleukin 8, a second neutrophil-activating protein. NH2-terminal amino acid sequence identity with melanoma growth stimulatory activity. Schröder, J.M., Persoon, N.L., Christophers, E. J. Exp. Med. (1990) [Pubmed]
  10. A mutant of melanoma growth stimulating activity does not activate neutrophils but blocks erythrocyte invasion by malaria. Hesselgesser, J., Chitnis, C.E., Miller, L.H., Yansura, D.G., Simmons, L.C., Fairbrother, W.J., Kotts, C., Wirth, C., Gillece-Castro, B.L., Horuk, R. J. Biol. Chem. (1995) [Pubmed]
  11. Expression profiling of palmitate- and oleate-regulated genes provides novel insights into the effects of chronic lipid exposure on pancreatic beta-cell function. Busch, A.K., Cordery, D., Denyer, G.S., Biden, T.J. Diabetes (2002) [Pubmed]
  12. Constitutive expression of growth-related oncogene and its receptor in oligodendrogliomas. Robinson, S., Cohen, M., Prayson, R., Ransohoff, R.M., Tabrizi, N., Miller, R.H. Neurosurgery (2001) [Pubmed]
  13. Chemokine growth-regulated-alpha: a possible role in the pathogenesis of endometriosis. Szamatowicz, J., Laudański, P., Tomaszewska, I., Szamatowicz, M. Gynecol. Endocrinol. (2002) [Pubmed]
  14. Growth-related oncogene produced in human breast cancer cells and regulated by Syk protein-tyrosine kinase. Li, J., Sidell, N. Int. J. Cancer (2005) [Pubmed]
  15. The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. Melillo, R.M., Castellone, M.D., Guarino, V., De Falco, V., Cirafici, A.M., Salvatore, G., Caiazzo, F., Basolo, F., Giannini, R., Kruhoffer, M., Orntoft, T., Fusco, A., Santoro, M. J. Clin. Invest. (2005) [Pubmed]
  16. PAK1 kinase is required for CXCL1-induced chemotaxis. Wang, D., Sai, J., Carter, G., Sachpatzidis, A., Lolis, E., Richmond, A. Biochemistry (2002) [Pubmed]
  17. Constitutive expression of growth regulated oncogene (gro) in human colon carcinoma cells with different metastatic potential and its role in regulating their metastatic phenotype. Li, A., Varney, M.L., Singh, R.K. Clin. Exp. Metastasis (2004) [Pubmed]
  18. Constitutive IkappaB kinase activity correlates with nuclear factor-kappaB activation in human melanoma cells. Yang, J., Richmond, A. Cancer Res. (2001) [Pubmed]
  19. Gene expression profiling reveals cross-talk between melanoma and fibroblasts: implications for host-tumor interactions in metastasis. Gallagher, P.G., Bao, Y., Prorock, A., Zigrino, P., Nischt, R., Politi, V., Mauch, C., Dragulev, B., Fox, J.W. Cancer Res. (2005) [Pubmed]
  20. IL-8/CXCL8 and growth-related oncogene alpha/CXCL1 induce chondrocyte hypertrophic differentiation. Merz, D., Liu, R., Johnson, K., Terkeltaub, R. J. Immunol. (2003) [Pubmed]
  21. Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2. Kershaw, M.H., Wang, G., Westwood, J.A., Pachynski, R.K., Tiffany, H.L., Marincola, F.M., Wang, E., Young, H.A., Murphy, P.M., Hwu, P. Hum. Gene Ther. (2002) [Pubmed]
  22. Cell surface heparan sulfate participates in CXCL1-induced signaling. Wang, D., Sai, J., Richmond, A. Biochemistry (2003) [Pubmed]
  23. The melanoma growth stimulatory activity receptor consists of two proteins. Ligand binding results in enhanced tyrosine phosphorylation. Cheng, Q.C., Han, J.H., Thomas, H.G., Balentien, E., Richmond, A. J. Immunol. (1992) [Pubmed]
  24. The CXC chemokines growth-regulated oncogene (GRO) alpha, GRObeta, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor. Ahuja, S.K., Murphy, P.M. J. Biol. Chem. (1996) [Pubmed]
  25. Conformational constraining of inactive and active States of a seven transmembrane receptor by metal ion site engineering in the extracellular end of transmembrane segment v. Rosenkilde, M.M., David, R., Oerlecke, I., Benned-Jensen, T., Geumann, U., Beck-Sickinger, A.G., Schwartz, T.W. Mol. Pharmacol. (2006) [Pubmed]
  26. CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. Wang, D., Wang, H., Brown, J., Daikoku, T., Ning, W., Shi, Q., Richmond, A., Strieter, R., Dey, S.K., DuBois, R.N. J. Exp. Med. (2006) [Pubmed]
  27. Melanoma growth-stimulatory activity/GRO decreases collagen expression by human fibroblasts. Regulation by C-X-C but not C-C cytokines. Unemori, E.N., Amento, E.P., Bauer, E.A., Horuk, R. J. Biol. Chem. (1993) [Pubmed]
  28. Postcapillary venule endothelial cells in kidney express a multispecific chemokine receptor that is structurally and functionally identical to the erythroid isoform, which is the Duffy blood group antigen. Hadley, T.J., Lu, Z.H., Wasniowska, K., Martin, A.W., Peiper, S.C., Hesselgesser, J., Horuk, R. J. Clin. Invest. (1994) [Pubmed]
  29. Neutrophil-activating peptide 2 and gro/melanoma growth-stimulatory activity interact with neutrophil-activating peptide 1/interleukin 8 receptors on human neutrophils. Moser, B., Schumacher, C., von Tscharner, V., Clark-Lewis, I., Baggiolini, M. J. Biol. Chem. (1991) [Pubmed]
  30. Endothelin-1 induces CXCL1 and CXCL8 secretion in human melanoma cells. Mangahas, C.R., dela Cruz, G.V., Friedman-Jiménez, G., Jamal, S. J. Invest. Dermatol. (2005) [Pubmed]
  31. Upregulation of chemokine CXCL1/KC by leptospiral membrane lipoprotein preparation in renal tubule epithelial cells. Hung, C.C., Chang, C.T., Chen, K.H., Tian, Y.C., Wu, M.S., Pan, M.J., Vandewalle, A., Yang, C.W. Kidney Int. (2006) [Pubmed]
  32. Expression and regulation of chemokine receptors in human natural killer cells. Inngjerdingen, M., Damaj, B., Maghazachi, A.A. Blood (2001) [Pubmed]
  33. Chemokine levels in human liver homogenates: associations between GRO alpha and histopathological evidence of alcoholic hepatitis. Maltby, J., Wright, S., Bird, G., Sheron, N. Hepatology (1996) [Pubmed]
  34. Extremely low dose ionizing radiation up-regulates CXC chemokines in normal human fibroblasts. Fujimori, A., Okayasu, R., Ishihara, H., Yoshida, S., Eguchi-Kasai, K., Nojima, K., Ebisawa, S., Takahashi, S. Cancer Res. (2005) [Pubmed]
  35. Chemokines induce migrational responses in human breast carcinoma cell lines. Youngs, S.J., Ali, S.A., Taub, D.D., Rees, R.C. Int. J. Cancer (1997) [Pubmed]
  36. Autocrine regulation of interleukin-8 production in human monocytes. Browning, D.D., Diehl, W.C., Hsu, M.H., Schraufstatter, I.U., Ye, R.D. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) [Pubmed]
  37. Induction of the CXCL1 (KC) chemokine in mouse astrocytes by infection with the murine encephalomyelitis virus of Theiler. Rubio, N., Sanz-Rodriguez, F. Virology (2007) [Pubmed]
  38. Expression and migratory analysis of 5 human uveal melanoma cell lines for CXCL12, CXCL8, CXCL1, and HGF. Di Cesare, S., Marshall, J.C., Logan, P., Antecka, E., Faingold, D., Maloney, S.C., Burnier, M.N. Journal of carcinogenesis (2007) [Pubmed]
  39. Identification of a novel granulocyte chemotactic protein (GCP-2) from human tumor cells. In vitro and in vivo comparison with natural forms of GRO, IP-10, and IL-8. Proost, P., De Wolf-Peeters, C., Conings, R., Opdenakker, G., Billiau, A., Van Damme, J. J. Immunol. (1993) [Pubmed]
  40. Melanoma growth stimulatory activity enhances the phosphorylation of the class II interleukin-8 receptor in non-hematopoietic cells. Mueller, S.G., Schraw, W.P., Richmond, A. J. Biol. Chem. (1994) [Pubmed]
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