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FLASH GENE
Symbol CXCL1 contributors: mct - updated : 11-04-2020
HGNC name chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)
HGNC id 4602
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to murine Gro1
Homologene
FAMILY
  • intercrine alpha (chemokine CxC) family
  • ELR-CXC chemokine family
    • CATEGORY regulatory , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    text expressed on hepatic stellate cells (HSCs)
    basic FUNCTION
  • growth regulator
  • melanoma growth stimulating activity
  • may play a role in inflammation and exerts its effects on endothelial cells in an autocrine fashion
  • potent inducer of senescence in stromal fibroblasts (depending on functional TP53), having a role for cell survival and the malignant transformation of ovarian epithelial cells
  • CXCL1 and CXCL2 play important roles in the infiltration of neutrophils into the site of injection of necrotic cells
  • both CXCL1 and CXCR2 play an important role in chemokine expression and neutrophil infiltration following adenoviral corneal infection, but have a redundant role in the development of keratitis
  • mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation
  • novel role for CXCL1 in neutrophil recruitment via modulating T cell function and neutrophil-related bactericidal functions
  • CXCL1 and its receptor CXCR2 play a crucial role in host immune response by recruiting and activating neutrophils for microbial killing at the tissue site
  • CXCL1-Glycosaminoglycan (GAG) interactions provide stringent control over regulating chemokine levels and receptor accessibility and activation, and chemotactic gradients mediate cellular trafficking to the target site
  • tumor-derived CXCL1 contributes to tumor-associated neutrophils (TANs) infiltration in lung cancer which promotes tumor growth
  • plays a pivotal role in the host immune response by recruiting and activating neutrophils for microbial killing at the tissue site
  • chemotactic cytokine known to regulate cancer progression and invasion
  • by inducing glycolysis, CXCL1 plays a crucial role in both cancer progression and metastasis in Colorectal cancer patients
  • inflammation-induced CXCL1 triggers neuroblast senescence, thus suppressing new neuron development in the hippocampus
  • novel role of CXCL1 and CXCL2 in promoting mo-MDSC (monocytic myeloid-derived suppressor cells) generation by favoring the differentiation of bone marrow cells in tumor-bearing conditions, which suggests that inhibition of CXCL1 and CXCL2 could decrease mo-MDSC generation and improve host immunosurveillance
  • was produced mainly by TNF-stimulated endothelial cells (ECs) and pericytes and supported luminal and sub-EC neutrophil crawling
  • is a neutrophil chemokine involved in the pathogenesis of chronic obstructive pulmonary disease (COPD)
  • CXCL1 mediates adiponectin-induced angiogenesis in ovarian cancer
  • critical factor in inflammatory diseases and tumor progression
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • plays an important role in leukocyte recruitment induced by both CXCL1 and CXCL2
  • is at least partially effective through LSP1 and the phosphorylation of MAPK14
  • excessive CXCL1 expression in IL6ST-deficient endothelial cells augments neutrophil adhesion but hinders migration, most likely by disrupting chemotactic gradients
  • serine-phosphorylated STAT1 bound to the promoters of the CXCL1 and CXCL2 genes and NFKB1 and STAT1 control CXCL1 and CXCL2 gene transcription
  • IL1B-mediated regulation of the CXCL1 and CXCL2 genes in pancreatic beta-cells requires stimulus-induced changes in histone chemical modifications
  • TNF induces CXCL1 expression through the JNK, MAPK14 and PI-3K/Akt signaling pathways in human pulmonary epithelial cells
  • role for CXCL1 and IL8 in CF lung disease severity and identify STAT3 as a modulating pathway
  • CXCL1 and CXCL2 regulate NLRP3 inflammasome activation via G-Protein-Coupled Receptor CXCR2
  • BSG regulates CXCL1 release in hepatic stellate cells (HSCs) by PI3K/AKT1 signaling
  • CXCL1 and CXCL2 act in a sequential manner to guide neutrophils through venular walls as governed by their distinct cellular sources
  • N4BP1 controls the proper function of keratinocytes and neutrophils by negatively regulating JUNB, FOSB, and CXCL1, respectively, and that is critical for psoriasis prevention
    • cell & other
    REGULATION
    activated by RAS
    induced by Prokineticin 1 (induces CCL4, CXCL1 and IL8 in monocytes but not in macrophages and dendritic cells)
    IL17 (IL17 is a weak stimulus for transcription of the CXCL1 gene, it strongly potentiates message accumulation via stabilization when the mRNA is transcribed in cells stimulated with TNF)
    Other activation of monocytes in patients with rheumatoid arthritis
    IL1A regulates CXCL1, CXCL10, and ICAM1 in network form in oral keratinocytes
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in ulcerative colitis, osteoarhtritis
    tumoral     --over  
    in ovarian cancer
    tumoral       gain of function
    in ER&8209;negative Breast cancer tissues and cell lines compared with ER&8209;positive tissues and cell lines
    tumoral     --over  
    obese patients with prostate cancer have increased epithelial CXCL1 expression
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • sputum CXCL1 levels is a potentially better diagnostic marker for chronic obstructive pulmonary disease (COPD) than sputum CXCL8 levels, which is explained by that CXCL1 production in bronchial epithelial cells is less affected by therapeutic anti-inflammatory agents
  • CXCL1 may serve as a new biomarker for ColoRectal Cancer
  • urine CXCL1 is a promising, non-invasive molecular marker for tumor detection and outcome prediction in patients with bladder cancer (BCa)
  • urinary CXCL1 is a new non-invasive predictor of IgAN progression
    • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    may serve as a potential therapeutic target in ER‑negative Breast cancer
    cancerreproductiveovary
    therapeutic target as well as a diagnostic marker in ovarian cancer
    cancer  
    targeting CXCL1 for cancer therapy would be applicable to a large portion of human tumors with mutant TP53, but the exploration of CXCL1 as a potential target should take the mutation status of TP53 into consideration
    cancerreproductivebreast
    CXCL1-based therapy might become a novel strategy for breast cancer metastasis prevention
    cancerdigestivecolon
    CXCL1 may serve as a potential therapeutic target for CRC treatment
    cancerdigestivestomach
    CXCL1 produced in T- lymphatic endothelial cells (LECs) represents a potentially promising target for treating gastric cancer
    ANIMAL & CELL MODELS