CD9

Fig1. A schematic model illustrating negative regulation of macrophage activation by the CD9-enriched microdomain. (Yoshito Takeda, 2015)

What is CD9 protein?

CD9 gene (CD9 molecule) is a protein coding gene which situated on the short arm of chromosome 12 at locus 12p13. This gene encodes a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Tetraspanins are cell surface glycoproteins with four transmembrane domains that form multimeric complexes with other cell surface proteins. The encoded protein functions in many cellular processes including differentiation, adhesion, and signal transduction, and expression of this gene plays a critical role in the suppression of cancer cell motility and metastasis. The CD9 protein is consisted of 228 amino acids and CD9 molecular weight is approximately 25.4 kDa.

What is the function of CD9 protein?

It plays a crucial role in various cellular processes such as differentiation, adhesion, and signal transduction. The expression of CD9 is critical in the suppression of cancer cell motility and metastasis. It is also an integral membrane protein associated with integrins, which helps regulate processes like sperm-egg fusion, platelet activation and aggregation, and cell adhesion. Furthermore, CD9 is involved in cell adhesion, cell motility, and tumor metastasis, and it is present at the cell surface of oocytes, where it is key in sperm-egg fusion, possibly by organizing multiprotein complexes and the morphology of the membrane required for the fusion.

CD9 Related Signaling Pathway

CD9 is involved in the signaling pathway that regulates interferon gene stimulating factor (STING). STING can form oligomers and enter extracellular vesicles (EVs) after activation, and STAM protein can bind STING oligomers and transport them to EVs, thereby negatively regulating STING signaling pathways. CD9 exists in the extracellular vesicle membrane and is involved in material transfer and communication between cells. By binding to E-cadherin and b-catenin, it affects exosomal output of b-catenin, thereby stimulating the wnt signaling pathway. In B-line acute lymphoblastic leukemia (B-ALL) cells, CD9 activates the PI3K/AKT signaling pathway through direct interaction with PI3K-P85, which may have important implications for disease development and treatment.

Fig2. Schematic illustrating that CD9/ADAM17 axis plays a key role in keratinocyte migration via activation of EGFR/ERK signaling pathway. (Jie Liu, 2019)

CD9 Related Diseases

In tumors, CD9 may act as a tumor promoter or inhibitor, affecting tumor genesis, metastasis, and angiogenesis. For example, in acute myeloid leukemia (AML), especially acute promyelocytic leukemia (APL), CD9 is often highly expressed. In addition, CD9 expression levels are highly associated with the risk of recurrence of acute lymphoblastic leukemia (ALL). CD9 is involved in membrane fusion, viral budding and particle release, and is closely related to various viral infections and morbidity. As a host factor, CD9 participates in the infection process of pathogens and is related to the occurrence of inflammation.

Bioapplications of CD9

CD9 exists in plasma membrane, endocytosis, nucleus, and small extracellular vesicles, and is released into body fluids. Cd9 is one of the classic markers of exosomes, and has potential application value for prognostic monitoring, drug targeted delivery system, and early diagnosis and screening of diseases. Cd9-related clinical trials involving hematologic tumors, type 1 diabetes, solid tumors, systemic sclerosis, etc., have demonstrated its potential application in disease diagnosis, treatment, prognostic monitoring, and early screening. As a host factor, CD9 is involved in the infection process of a variety of pathogens, including membrane fusion, budding and particle release of viruses, and is closely related to a variety of viral infections and morbidity.