An Overview of CX3CL1 Protein


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In recombinant human FRACTALKINE/CX3CL1, CX3CL1 is a 373 amino acid large cytokine protein, which contains multiple domains, and is the only known member of the CX3C chemokine family. It is also commonly called fractalkine (in humans) and neurotactin (in mice). The polypeptide structure of CX3CL1 is different from the typical structure of other chemokines. For example, the characteristic N-terminal cysteine ​​intervals are different; there are three amino acids in CX3CL1 to distinguish the initial cysteine, none of the CC chemokines, and only one intermediate amino acid in the CXC chemokines. CX3CL1 is a long protein (containing 373 amino acids in the human body), with an extended mucin-like stem and chemokine domain. The mucin-like stem allows it to bind to the surface of certain cells. However, a soluble (90kD) form of this chemokine was also observed. Soluble CX3CL1 effectively chemisorbs T cells and monocytes, and the cells bind chemokines to promote the strong adhesion of leukocytes to activated endothelial cells, where it is mainly expressed. CX3CL1 triggers its adhesion and migration functions by interacting with the chemokine receptor CX3CR1. Its genes are located on human chromosome 16 and some CC chemokines Fractalkine called CCL17 and CCL22 are usually found throughout the brain, especially in nerve cells, and its receptors are known to exist on microglia. It was also found that it is necessary for microglia migration. CX3CL1 is also upregulated in the hippocampus within a short time window after spatial learning. The purpose may be to regulate glutamate-mediated neurotransmission. This suggests that chemokines may play a role in the protective process of synaptic scaling. In addition to the dual functions of adhesion and chemotaxis, CX3CL1 may play an anti-tumor or pro-tumor role in the growth, invasion and metastasis of various malignant tumors (including pancreatic cancer). However, there is no research to prove whether CX3CL1 has an effect on the glucose metabolism of pancreatic cancer. The study of the tumor cell sugar metabolism mechanism will help to discover new therapeutic targets.


 


Clinical application


Recombinant human FRACTALKINE/CX3CL1 can be used in tumor treatment and prognostic marker detection research. Principle CX3CL1 has the function of enhancing glycolysis of pancreatic cancer cells, promoting their glucose uptake and lactate secretion. At the same time, previous studies have demonstrated that CX3CL1 can activate increased levels of HIF-1a in cells. Combined with the previous important regulatory role of HIF-1a in tumor glucose metabolism. CX3CR1, a specific receptor for CX3CL1, is expressed in a pancreatic cancer cell line; after interference with siRNA, it can be found that CX3CL1 promotes glycolysis of pancreatic cancer cells through CX3CR1; at the same time, CX3CL1 can activate PI3K/Akt and MAPK signals Pathway promotes the expression of HIF-1a; after interference with siRNA, CX3CL1 can be found to promote the glycolysis of pancreatic cancer cells by regulating the expression of HIF-1a; CX3CL1 can promote the expression of the key enzyme of the glycolysis pathway, GLUT-1, HIF-1a In it its important regulatory role. Conclusion The CX3CL1/CX3CR1 axis enhances glycolysis of pancreatic cancer cells by activating PI3K/Akt and MAPK signaling pathways to promote HIF-1a expression; CX3CL1/CX3CR1/HIF-1a signaling pathway is an important mechanism of energy metabolism in pancreatic cancer cells, It may become a potential target for the treatment of pancreatic cancer.


 


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