Multi-faceted Properties of B4GalT1
Beta-1,4-Galactosyltransferase 1 (B4GalT1) belongs to the galactosyltransferase (GalT) family of enzymes that transfer galactose from uridine-diphosphate-α-D-galactose (UDP-Gal) to an acceptor sugar molecule. B4GalT1 is a critical enzyme in galactose metabolism.
One of the first GalT to be characterized biochemically, B4GalT1, was also involved in lactose production by interacting with α-lactalbumin during lactation1. However, more evidence has surfaced over the years illustrating B4GalT1’s role in other physiological processes such as aging2.
The Intimate Relationship Between B4GalT1 and Human Cancers
Several new studies have linked B4GalT1 expression to some forms of cancer. B4GalT1 was recently found to be involved in the proliferation and maintenance of cancer stem cells of lung adenocarcinoma3. Another study reported that high B4GalT1 expression in bladder cancer patients was also observed to correlate with low overall survival and expression of inhibitory receptor signals PD-1 and CTLA4. The effectiveness of adjuvant chemotherapy was also found to be higher in bladder cancer patients with lower expression levels of B4GalT14. Elevated B4GalT1 levels were also seen in megakaryocytes from myeloproliferative neoplasms5. Therefore B4GalT1 seems to play an essential role in human cancers, although more work has to be done to thoroughly examine the underlying mechanisms contributing to this relationship.
Targeting B4GalT1 for the Treatment of Glioblastoma
Glioblastoma multiforme (GBM), also known as glioblastoma, is the most aggressive and common form of glioma (a tumor that occurs in the brain and spine)6. Glioblastoma is a fast-growing, grade 4 glioma. Most patients with glioblastoma typically do not survive for more than a year. Due to the tumor’s complexity, glioblastoma remains an incurable disease, and treatment options are still relatively limited.
The involvement of B4GalT1 in glioblastoma is relatively unknown. However, a group of researchers reported for the first time that B4GalT1 expression was elevated in glioblastoma tumor tissue and human primary glioblastoma cells (U87)7. By reducing the expression of B4GalT1 in vitro, the proliferative and migratory capacity of U87 cells was suppressed. Mice injected with U87 cells expressing lower levels of B4GalT1 developed significantly smaller tumors and had a better survival rate than mice injected with normal U87 cells. They also discovered that underlying this phenomenon was that lower B4GalT1 expression induces apoptosis and autophagy of glioblastoma both in vitro and in vivo, therefore promoting cancer cell death. Hence, B4GalT1 plays critical role in regulating glioblastoma development. Targeting B4GalT1 for the treatment of glioblastoma is a highly viable approach that has to be further validated.
BellBrook’s Transcreener UDP2 Assay is a universal UDP detection HTS assay that utilizes a fluorescence-based method to measure glycosyltransferase activity by detecting UDP production.
How the Transcreener UDP2 Assay can facilitate B4GalT1 research:
- Evaluate enzymatic activity
- Screen for small molecule inhibitors
- Determine inhibitor potency/ IC50 values
- Profile inhibitor selectivity
- Support mechanistic studies
- Qasba, P. K., Ramakrishnan, B. & Boeggeman, E. Structure and Function of β-1,4-Galactosyltransferase. Curr Drug Targets 9, 292–309 (2008).
- Kremer, J., Brendel, C., Mack, E. K. M. & Mack, H. I. D. Expression of β-1,4-galactosyltransferases during Aging in Caenorhabditis elegans. GER 66, 571–581 (2020).
- De Vitis, C. et al. B4GALT1 Is a New Candidate to Maintain the Stemness of Lung Cancer Stem Cells. Journal of Clinical Medicine 8, 1928 (2019).
- Xie, H. et al. B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscle-invasive bladder cancer patients. BMC Cancer 18, 590 (2018).
- Di Buduo, C. A. et al. Increased B4GALT1 expression is associated with platelet surface galactosylation and thrombopoietin plasma levels in MPNs. Blood 137, 2085–2089 (2021).
- Holland, E. C. Glioblastoma multiforme: The terminator. Proc Natl Acad Sci U S A 97, 6242–6244 (2000).
- Wang, P., Li, X. & Xie, Y. B4GalT1 Regulates Apoptosis and Autophagy of Glioblastoma In Vitro and In Vivo. Technol Cancer Res Treat 19, 1533033820980104 (2020).