Carbohydrates are not only important energy sources for life activities, but also store important biological information in the glycogroup (glycan structure), which participates in regulating cell fate, energy supply, and the balance between health and disease.
As intracellular conditions (metabolic stress, growth factors, cytokines) are stimulated, the glycan structure will undergo aberrant glycosylation modifications due to remodeling, leading to disorders in intercellular communication, proliferation, differentiation, and survival processes, and subsequently leading to disease.
Galectin is an endogenous glycan-binding protein, which is an important translator that converts glycan information into biological programs, and is involved in tumorigenesis.
The core structure of galectin is the carbohydrate recognition domain (CRD), which is used to bind Glycans. According to the differences in CRD, it can be divided into three subfamilies:
The expression and subcellular localization of different subtypes vary greatly in different cell types and are dynamically regulated by physiological and pathological signals.
| Cat# | Product Name | Inquiry |
| XGB1042 | Galectin-1 human | Inquiry |
| XGB1043 | Galectin-3 human | Inquiry |
| XGB1044 | Galectin-7 human | Inquiry |
| XGB1045 | Galectin-8 from rat | Inquiry |
| XLC-103-10Q | Human galectin 3C-S (Gal 3C-S) lectin, E. coli, Recombinant | Inquiry |
| XLC-103-11Q | Human galectin 3 (Gal 3) lectin, E. coli, Recombinant | Inquiry |
| XLC-103-12Q | Human galectin 7-S (Gal 7-S) lectin, E. coli, Recombinant | Inquiry |
| XLC-103-13Q | Human galectin 9 (Gal 9) lectin, E. coli, Recombinant | Inquiry |
| XLC-103-8Q | Human galectin 1-S (Gal1-S) lectin, E. coli, Recombinant | Inquiry |
| XLC-103-9Q | Human galectin 1 (Gal 1) lectin, E. coli, Recombinant | Inquiry |
During the development of tumors, abnormal glycan information is mainly "translated" by galectin-1, galectin-3, and galectin-9 (9 is less common), which promotes tumor development through different mechanisms.
It is upregulated in the majority of tumour tissues and stroma, and it has been proposed as a marker for bad prognosis in breast cancer, colon cancer, lung cancer, prostate cancer and melanoma.
Galectin-1 drives epithelial-mesenchymal transition (EMT) of tumour cells in gastric cancer and hepatocellular carcinoma via activation of the Hedgehog signalling pathway, down-regulation of E-cadherin, and induction of the αvβ3-dependent Akt signaling pathway. It will affect the therapeutic effects of Solafeni and Doxorubicin.
Galectin-1 controls proliferation, invasion and metastasis in pancreatic cancer.
Silencing of galectin-1 in prostate cancer inhibits androgen receptor (AR) and AKT signaling, which in turn inhibits the migration and invasion of prostate cancer progenitor cells.
Galectin-3 can drive epidermal growth factor receptor (EGFR) activation in epithelial cancer through its binding to the transmembrane glycoprotein mucin 1 (MUC1), and tumour cell proliferation via the activation of ERK1/2 and Akt signalling pathway.
In breast cancer, the N-glycan structure on EGFR can drive the exposure of galectin-3’s special sugar epitopes and regulate EMT and metastasis of tumour cells.
Galectin-3 is a member of the Tf antigen expressed by metastatic tumour cells in lung cancer, and can drive the formation of metastatic ecological niches, the clustering of homotypic and heterotypic antigens, and the generation of emboli.
Galectin-3 binding to Tf antigen expressed by metastatic tumor cells in lung cancer can promote the establishment of metastatic ecological niche, the aggregation of homotypic and heterotypic antigens, and the generation of embolism.
Galectin-3 drives tumor cell proliferation and migration in oral squamous cell carcinoma through Wnt/β-catenin signaling pathway.
Galectin-3 in colorectal cancer works in concert with KRAS gene to promote proliferation and survival of cells, and enhances cell invasiveness through the Raf-MEK-ERK signaling pathway.
Fig. 1 Galectins reprogramme tumour landscapes in the tumour microenvironment. (Mariño, et al., 2023)
Abnormally newly formed blood vessels can provide nutrients for tumors, and galectins have angiogenic activity.
Galectin-1 can attach to N-glycans of vascular endothelial growth factor (VEGFR2) and trigger its phosphorylation for angiogenesis through the activation of Akt and ERK1/2 signaling pathways, especially in anti-VEGF therapy.
Interaction with transmembrane glycoprotein neuropilin 1 (NRP1) increases vascular permeability in addition to inducing angiogenesis.
Galectin-1 binds not only glycans and glycoproteins, but also mRNA of VEGF-A, early growth response protein 1 (EGR1), and laminin α5 to regulate angiogenesis.
When bound to N-glycans on αvβ3 and VEGFR, it can promote angiogenesis, while maintaining the expression of these two types of receptors on endothelial cells (EC).
In the tumor microenvironment, galectins act on multiple types of cells to shape an immunosuppressive environment,
Several galectins regulate recruitment, differentiation and proliferation of immunosuppressive cells M2 macrophages, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSC).
| Immunosuppressive Cells | Galectins Involved in Regulation |
| M2 macrophages | Galectin-1, galectin-3 and galectin-9 induce recruitment and differentiation |
| MDSC | Galectin-3 induces expansion |
| Tregs | Galectin-1 and galectin-9 induce expansion and differentiation |
For anti-tumor immune cells, galectin-1 and galectin-9 induce apoptosis of Th1, Th17, and CD8+ T cells. Galectin-3 inhibits NK cell-mediated cytotoxicity and can also form glycoprotein lattices to limit the interaction between T-cell receptor (TCR) and CD8 to inhibit anti-tumor immune responses.
Moreover, galectins can also act as co-inhibitory molecules and ligands of immune checkpoints to promote the transmission of immunosuppressive models:
Galectins participate in tumorigenesis through multiple mechanisms and also hinder tumor treatment.
However, developing a treatment strategy specifically for it may show good clinical results in terms of both suppressing tumors and optimizing other treatment options.
Reference
