Molecule Information

General Information of the Molecule (ID: Mol04389)

• Name: C-C motif chemokine 20 (CCL20) ,Homo sapiens
• Synonyms: Beta-chemokine exodus-1; CC chemokine LARC; Liver and activation-regulated chemokine; Macrophage inflammatory protein 3 alpha; Small-inducible cytokine A20
• Molecule Type: Protein
• Gene Name: CCL20
• Gene ID: 6364
• Sequence:
  MCCTKSLLLAALMSVLLLHLCGESEAASNFDCCLGYTDRILHPKFIVGFTRQLANEGCDI
  NAIIFHTKKKLSVCANPKQTWVKYIVRLLSKKVKNM
• Function: Acts as a ligand for C-C chemokine receptor CCR6. Signalsthrough binding and activation of CCR6 and induces a strong chemotacticresponse and mobilization of intracellular calcium ions. The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendriticcells , effector/memory T-cells and B-cells and plays an importantrole at skin and mucosal surfaces under homeostatic and inflammatoryconditions, as well as in pathology, including cancer and variousautoimmune diseases . CCL20 acts as a chemotacticfactor that attracts lymphocytes and, slightly, neutrophils, but notmonocytes . Involved in therecruitment of both the pro-inflammatory IL17 producing helper T-cells and the regulatory T-cells to sites of inflammation.Required for optimal migration of thymic natural regulatory T cells and DN1 early thymocyte progenitor cells . C-terminal processed forms have been shown to be equally chemotacticallyactive for leukocytes . Positively regulates spermmotility and chemotaxis via its binding to CCR6 which triggers Ca2+mobilization in the sperm which is important for its motility. Inhibits proliferation of myeloidprogenitors in colony formation assays . May beinvolved in formation and function of the mucosal lymphoid tissues byattracting lymphocytes and dendritic cells towards epithelial cells . Possesses antibacterial activity towards E.coli ATCC 25922and S.aureus ATCC 29213 .{ECO:0000250|UniProtKB:O89093, ECO:0000269|PubMed:11035086,ECO:0000269|PubMed:11352563, ECO:0000269|PubMed:12149255,ECO:0000269|PubMed:20068036, ECO:0000269|PubMed:23765988,ECO:0000269|PubMed:25122636, ECO:0000269|PubMed:9038201,ECO:0000269|PubMed:9129037, ECO:0000303|PubMed:21376174}.
• Uniprot ID: CCL20_HUMAN
• Ensembl ID: ENSG0000011500913
• HGNC ID: HGNC:10619

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Daunorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] [1]

• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Resistant Drug: Daunorubicin
• Molecule Alteration: Expression; Up-regulation
• Experiment for Molecule Alteration: ELISA assay
• Mechanism Description: Our study has identified CCL20 as a pivotal factor in the promotion of chemoresistance in AML cells by M2 macrophages. The chemotherapeutic agent daunorubicin induces a marked increase in ROS and lipid peroxidation levels within AML cells. This is accompanied by the inhibition of the SLC7A11/GCL/GPX4 signaling axis, elevated levels of intracellular free iron, disrupted iron metabolism, and consequent mitochondrial damage, ultimately leading to ferroptosis. Notably, CCL20 enhances the ability of AML cells to maintain iron homeostasis by upregulating SLC7A11 protein activity, mitigating mitochondrial damage, and inhibiting ferroptosis, thereby contributing to chemotherapy resistance. Furthermore, in vivo experiments demonstrated that blocking CCL20 effectively restores the sensitivity of AML cells to daunorubicin chemotherapy.

References

• Ref 1: M2 macrophages secrete CCL20 to regulate iron metabolism and promote daunorubicin resistance in AML cells. Life Sci. 2025 Jan 15;361:123297.