C1GALT1

What is C1GALT1 Protein?

C1GALT1, often called core 1 synthase, is like a sugar-adding maestro for proteins. This enzyme plays a big role in O-glycosylation, which is a really important step for creating the core structure of mucin-type O-glycans. Basically, it moves a sugar called galactose onto a specific spot, creating a structure essential for many other sugars that decorate cell surfaces and proteins. C1GALT1 is important in things like forming blood vessels, making platelets, and keeping kidneys working right. When it doesn’t work as it should, it can be linked to diseases like IgA nephropathy and hypersensitivity vasculitis. In cancer, C1GALT1 affects tumor growth, spread, and treatment resistance by changing how certain proteins are sugar-coated. Its activity can tie into how aggressive a tumor is and a patient’s outlook, making it a big deal in cancer biology and other related diseases.

What is the Function of C1GALT1 Protein?

C1GALT1, known as core 1 synthase, plays a crucial role in the O-glycosylation process by transferring galactose onto N-acetylgalactosamine, forming the Galβ1-3GalNAcαSer/Thr structure. This structure is a precursor for many extended O-glycans on cell surfaces and secretory glycoproteins. C1GALT1 is vital for various biological functions such as blood vessel formation, platelet production, and kidney development. It’s also involved in modulating the O-glycosylation of tumor-related proteins, impacting tumor growth, invasion, metastasis, and resistance to therapies, linking it closely with clinical outcomes. Furthermore, its function is influenced by its molecular chaperone, Cosmc, essential for proper folding and activity of T-synthase. Abnormal O-glycosylation is associated with cancer and other pathological states, highlighting C1GALT1’s pivotal role in these processes. Thus, C1GALT1 is significant in protein post-translational modification, cancer biology, and the progression of related diseases.

C1GALT1 Related Signaling Pathway

C1GALT1 protein is crucial in several signaling pathways, particularly in cancer biology and abnormal glycosylation. As an essential enzyme, C1GALT1 helps construct the core structure of mucin-type O-glycans, playing a big role in controlling cancer progression, invasion, and resistance to therapies. Its unusual expression is linked with various cancers like those in the respiratory and gastrointestinal systems. By affecting O-glycosylation, it aids in the formation of cancer-related carbohydrate antigens and impacts processes like epithelial-mesenchymal transition. In cancers like cholangiocarcinoma, C1GALT1 influences disease advancement by activating pathways like AKT/ERK. So, it’s a prime target for studying and treating related diseases.

C1GALT1 Related Diseases

C1GALT1 protein is closely linked to a variety of diseases, with a notable connection to the progression of various cancers. It plays a crucial role in forming the core structure essential for mucin-type O-glycans. Its abnormal expression is associated with aggressive cancer traits like proliferation, invasion, metastasis, and resistance to radiation and drugs. For instance, in gastrointestinal cancers, high C1GALT1 levels are linked to more aggressive colorectal cancer characteristics and promote invasiveness in cell lines like HCT116 and SW480. It may act differently in pancreatic cancer, where its loss seems to aid tumor growth and spread. In reproductive and endocrine cancers, C1GALT1 boosts breast cancer cell proliferation and influences ovarian cancer cell glycoproteins, impacting tumor behavior and growth. Moreover, in head and neck cancers, it alters the O-glycosylation of EGFR, affecting malignant traits. Interestingly, its abnormal expression is also tied to autoimmune disorders, highlighting C1GALT1 as a pivotal player in multiple disease pathways and a potential target for research and therapeutic interventions.

Bioapplications of C1GALT1

Recombinant C1GALT1 protein plays a significant role in scientific research, industrial production, and medical studies. In research, C1GALT1 is a crucial glycosyltransferase that controls the synthesis of O-linked mucin-type glycans, and its expression changes in cancer cells are widely studied for their impact on various cancers. In the industrial field, recombinant C1GALT1 is produced using expression systems like HEK293 cells, and it’s purified with His tags, which is vital for understanding its structure and function, contributing to quality control in biopharmaceuticals. Medically, C1GALT1 is closely linked to the development of various malignant tumors, and its overexpression in epithelial cancers is associated with poor prognosis. This makes it a key target for studying disease mechanisms and developing novel therapies. Thus, recombinant C1GALT1 protein holds valuable potential in advancing scientific knowledge and clinical applications.

Case Study 1: Wan Y. et al. Cell Death Dis. 2023

We know that glycosylation tweaks most cell membrane proteins, but what exactly it does is still pretty unclear. One enzyme grabbing attention is β1,3-galactosyltransferase (C1GalT1), a key player in crafting O-linked mucin-type glycans, and it’s often found in high amounts in many epithelial cancers. When we dial down its presence in human colon cancer cells, we see stark shifts in the glycosylation of cell membrane proteins, particularly those interacting with galectin-3 and macrophage lectin (MGL). This suppression hampers cancer cell growth, adhesion, and migration, while also enhancing interaction and phagocytosis of cancer cells by macrophages. Fascinatingly, in chick embryo experiments, cancers overexpressing C1GalT1 spawned larger tumors, notably bolstered by galectin-3. On the flip side, more macrophages and dendritic cells moved into the tumor environment in certain genetically tweaked mice. Thus, it seems like C1GalT1 could be a big player in how cancers advance and dodge the immune system.

• 
  Fig1. shRNA C1GalT1 transfection led to substantial reduction of C1GalT1 in SW620.
• 
  Fig2. C1GalT1 suppression reduces galectin-3-mediated EGFR phosphorylation in cell response to EGF in HCT116F3 cells.

Case Study 2: Li J. et al. Circulation. 2020

C1GALT1, an enzyme creating the T antigen by adding galactose, is frequently overexpressed in colorectal cancer, linked to worse survival outcomes. Its overexpression boosts tumor growth, migration, and metastasis. Through our research, we discovered that C1GALT1 alters O-glycans on FGFR2, a key receptor in colon cancer cells, leading to enhanced cancerous behaviors. Knockdown experiments showed that reducing C1GALT1 levels can curb these aggressive traits. Plus, using the FGFR inhibitor BGJ398 halted C1GALT1’s enhancement effects, suggesting C1GALT1 plays a significant role in the cancer’s progression through modifying glycosylation pathways.

• 
  Fig3. Western blots of C1GALT1 expression in paired normal (N) and tumor (T) tissue from colorectal cancer patients.
• 
  Fig4. Effects of C1GALT1 on cell migration.

• 
  Fig1. Regulation and action of C1GalT1 in biosynthesis of O-linked mucin-type glycans. (Yangu Wan, 2021)
• 
  Fig2. Inhibiting C1GALT1 raises Tn antigen levels while boosting sTn antigen and core 3 structure due to competition with ST6GalNAC and core 3 synthase, leading to lower core 1 structure levels. (Hong Tian, 2024)

C1GALT1 has several biochemical functions, for example, galactosyltransferase activity,glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase activity,metal ion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by C1GALT1 itself. We selected most functions C1GALT1 had, and list some proteins which have the same functions with C1GALT1. You can find most of the proteins on our site.

Function	Related Protein
transferase activity, transferring glycosyl groups	GXYLT1B,UGT5D1,UGT5F1,ST6GAL2A,GTDC1,PNP4B,UGT2B6,GALNTL4,ALG6,B3GNT5B
galactosyltransferase activity	B4GALT1,GALNT18A,DPY19L4,B3GNT5A,B3GNT9-PS,B3GALNT2,4931440L10Rik,GLT8D1,B3GNT5B,B4GALT7
transferase activity	NLK2,COQ2,PLK2B,EXT1C,PI4KAB,GXYLT2,HS6ST1A,UGT5C3,UGT1A5,NMT1A
glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase activity	C1GALT1A,C1GALT1C1,C1GALT1B
metal ion binding	KCND1,ZNF557,RIMS1,TRERF1,PC,ATP2B1B,RPP21,PPM1E,REV3L,ITGA10

C1GALT1 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 C1GALT1 here. Most of them are supplied by our site. Hope this information will be useful for your research of C1GALT1.