Helping Fight Ovarian Cancer with ST3GAL1 Inhibitors

Important functions such as cell–cell recognition, protein targeting, and cell adhesion taking place in the human body get carried out through a process known as sialylation. Sialylation is a common reaction that is catalyzed by a sialyltransferase (ST) enzyme with the goal of adding a sialic acid (monosaccharide) to a growing oligosaccharide forming a glycolipid or glycoprotein.

These same functions along with many others are negatively impacted in cancer patients leading to tumor progression and metastasis. Therefore, it comes as no shock that individuals with cancer have an abnormally high level of sialyltransferases (STs).

There are multiple types of STs named based on the linkage and function; specifically, their attachment of sialic acid to various terminal positions on a glycoprotein. For example, Beta-galactoside alpha-2,3-sialyltransferase 1 (ST3GAL1) is named as such due to the transfer of sialic acid from cytidine monophosphate-sialic acid to galactose-containing substrates.

Contribution of ST3GAL1 in Ovarian Cancer

Researchers have found an increased level of ST3GAL1 in ovarian cancers, which has been associated with resistance to chemotherapy and tumor progression.²

Since hypersialylation has been associated with metastatic cell behavior including invasion and enhanced cell survival, finding a ST3GAL1 inhibitor would be useful in preventing metastasis which is extremely necessary in ovarian cancer.² Typically, the disease has progressed and metastasized by the time it is diagnosed due to no specific symptoms or easy, reliable detection methods.

Of all cancers, ovarian is the fifth leading in cancer-related deaths.¹ As with many cancer types, there’s a higher survival rate if the disease is found early, and proper treatment occurs.

ST3GAL1 Inhibitor Assay 

Researchers have found a decrease in cell growth, migration, and invasion when ST3GAL1 is knockdown in ovarian cancer tissue culture cells.² While the search is on for discovering ST3GAL1 inhibitors in order to battle cancer, there is still much to learn. The Transcreener® AMP²/GMP² Assay is capable of detecting ST3GAL1 activity through direct detection of CMP. The enzyme converts CMP-sialic acid to sialic acid in order to create a galactose-containing substrate, forming CMP as a product that can be measured by using a specific antibody and tracer labeled with a fluorophore. This advantageous method can assist in the drug discovery by providing an HTS capable screening tool, and an effort to find ST3GAL1 inhibitors as an ovarian cancer treatment.

References

1. Coleman RL, Hennessy BT, Coleman RL, Markman M. Ovarian cancer. 2015;6736(June):433-440. doi:10.1016/S0140-6736(09)61338-6
2. Wu X, Zhao J, Ruan Y, Sun L, Xu C, Jiang H. Sialyltransferase ST3GAL1 promotes cell migration, invasion, and TGF-β1-induced EMT and confers paclitaxel resistance in ovarian cancer. Cell Death Dis. 2018;9(11). doi:10.1038/s41419-018-1101-0