LGALS9

Fig1. Structure and extracellular functions of galectins. (Victor L Thijssen, 2014)

What is LGALS9 Protein?

LGALS9 gene (galectin 9) is a protein coding gene which situated on the long arm of chromosome 17 at locus 17q11. The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. The protein encoded by this gene is an S-type lectin. It is overexpressed in Hodgkin's disease tissue and might participate in the interaction between the H&RS cells with their surrounding cells and might thus play a role in the pathogenesis of this disease and/or its associated immunodeficiency. The LGALS9 protein is consisted of 355 amino acids and LGALS9 molecular weight is approximately 39.5 kDa.

What is the Function of LGALS9 Protein?

LGALS9, also known as Galectin-9, is a member of the galactolectin family. Galactolectins are a class of proteins with carbohydrate binding activity, which can recognize and bind specific glycosylation structures. The functions of LGALS9 are diverse, including the regulation of cell adhesion, cell signaling, cell proliferation, and cell death. It plays a role in a variety of biological processes, such as immune response, inflammation, tumor development, and cell differentiation. LGALS9 may also be involved in regulating cellular metabolic processes, including glucose uptake and glycolysis, which may play an important role in metabolic reprogramming of tumor cells.

LGALS9 Related Signaling Pathway

In terms of signal transduction, LGALS9 can inhibit B cell receptor signaling. Studies have shown that it activates the Lyn protein by binding to the glycoprotein CD45, which in turn inhibits calcium signaling through a mechanism dependent on Lyn-CD22-SHP-1 and reduces B-cell activation. In terms of immune regulation, the expression of LGALS9 is associated with the regulation of type I interferon signaling pathway, interferon-gamma mediated signaling pathway, RIG-I like receptor signaling pathway, NF-κB signaling pathway, cytoplasmic DNA sensing pathway, and TNF signaling pathway. These pathways are important in both immune response and tumor development. In autoimmune diseases such as systemic lupus Erythematosus (SLE) and rheumatoid arthritis (RA), LGALS9 also plays a role in related signaling pathways.

LGALS9 Related Diseases

LGALS9 has been implicated in a variety of diseases, especially pathological states involving the immune system and tumor development. In autoimmune diseases such as systemic lupus Erythematosus (SLE) and rheumatoid arthritis (RA), LGALS9 is involved in regulating communication between immune cells, affecting the progression of the disease. In addition, the abnormal expression of LGALS9 in various types of cancer is closely related to the survival, proliferation, invasion and metastasis of tumor cells, and the change of its expression level can be used as a prognostic biomarker for some cancers, such as pancreatic cancer. Therefore, the multifaceted role of LGALS9 in pathology makes it an important target for research and potential therapeutic interventions.

Bioapplications of LGALS9

As an immunomodulatory protein, the relevant applications of LGALS9 are mainly concentrated in the field of biomedical research, especially in cancer therapy and immunomodulatory therapy. Although there are currently no drugs that directly target LGALS9 in widespread clinical use, LGALS9 has shown potential in the development of immune checkpoint inhibitors that may serve as new therapeutic targets to enhance anti-tumor activity by modulating the immune response. In addition, the expression patterns of LGALS9 in different cancers suggest its potential as a biomarker for disease surveillance and prognostic assessment. With further research on the function of LGALS9, novel therapeutic strategies targeting this protein may be developed in the future.

Case Study 1: Valerie R Wiersma, 2015

Oncogenic mutation of KRAS (Kirsten rat sarcoma viral oncogene homolog) in colorectal cancer (CRC) confers resistance to both chemotherapy and EGFR (epidermal growth factor receptor)-targeted therapy. Researchers uncovered that KRAS mutant (KRAS(mut)) CRC is uniquely sensitive to treatment with recombinant LGALS9/Galectin-9 (rLGALS9), a recently established regulator of epithelial polarity. Upon treatment of CRC cells, rLGALS9 rapidly internalizes via early- and late-endosomes and accumulates in the lysosomal compartment. Treatment with rLGALS9 is accompanied by induction of frustrated autophagy in KRAS(mut) CRC, but not in CRC with BRAF (B-Raf proto-oncogene, serine/threonine kinase) mutations (BRAF(mut)). In KRAS(mut) CRC, rLGALS9 acts as a lysosomal inhibitor that inhibits autophagosome-lysosome fusion, leading to autophagosome accumulation, excessive lysosomal swelling and cell death. This antitumor activity of rLGALS9 directly correlates with elevated basal autophagic flux in KRAS(mut) cancer cells.

Fig1. Time-dependent increase in lysosomal association of rLGALS9 in DLD-1 cells.

Fig2. Linear correlation analysis of the reduction in cell viability upon rLGALS9 treatment and increases in Cyto-ID signal upon rLGALS9 treatment.

Case Study 2: Andrew J Steelman, 2014

In the present study researchers examined the role of the Tim-3/galectin-9 pathway in glial activation in vitro. The effect of endogenous galectin-9 production on microglial activation was examined using cultures from wild-type and Lgals9 null mice. The ability for recombinant galectin-9 to promote microglia activation was also assessed. Tim-3 expression on microglia and BV2 cells was examined by qPCR and flow cytometry and its necessity in transducing the galectin-9 signal was determined. The results showed that Poly(I:C) stimulation increased galectin-9 expression in microglia and microglial-derived factors promoted galectin-9 up-regulation in astrocytes. Astrocyte-derived galectin-9 in turn enhanced microglial TNF production. Similarly, recombinant galectin-9 enhanced poly(I:C)-induced microglial TNF and IL-6 production.

Fig3. Primary mouse microglia were unstimulated (CTL) or stimulated with recombinant mouse galectin-9 or poly(I:C).

Fig4. TNF levels measured in the presence of increasing concentrations of recombinant mouse galectin-9.

LGALS9 has several biochemical functions, for example, carbohydrate binding,disaccharide binding,enzyme binding. Some of the functions are cooperated with other proteins, some of the functions could acted by LGALS9 itself. We selected most functions LGALS9 had, and list some proteins which have the same functions with LGALS9. You can find most of the proteins on our site.

LGALS9 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with LGALS9 here. Most of them are supplied by our site. Hope this information will be useful for your research of LGALS9.

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