Understanding How Notum Promotes Glypican-3 Shedding In Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), a solid tumor malignancy, causes approximately 1 million deaths annually, and therefore is considered one of the primary causes of cancer mortality in the world. HCC has proven to be exceedingly resistant to chemotherapy with little improvement in mortality rates in recent years. Like any cancer, to better diagnose, treat, and prevent HCC, we must gain a better understanding of the specific secreted factors that precisely relate to the disease. Recently, the proteoglycan family, proteins containing glycosaminoglycan (carbohydrate) chains, and the proteins that interact with them have been identified as possible therapeutic targets for a variety of cancer treatments. In HCC specifically, a secreted factor belonging to the proteoglycan family known as glypican-3 (GPC-3) is significantly overexpressed. GPC-3 has been shown to promote the growth of HCC cells through stimulation of the growth factor signaling pathway known as Wnt. We seek to understand to what enzymes and regulatory factors that facilitate the shedding (removal from cell’s surface) of GPC-3. To quantify the relationship between such factors and GPC-3, we have used an ELISA analysis. Once this relationship is thoroughly understood, we will be able to use the newfound specificity to determine a more precise treatment to regulate GPC-3 shedding in HCC. In our ambitions to understand GPC-3 shedding, it may lead others to develop a novel therapeutic approach for targeting this shedding in HCC