NOTUM (Wnt signaling)

NOTUM is a secreted protein that plays a crucial role in regulating the Wnt signaling pathway. The Wnt signaling pathway is involved in a wide range of biological processes, including embryonic development, tissue regeneration, and cancer progression. Dysregulation of the Wnt signaling pathway is associated with several human diseases, including cancer. Therefore, understanding the regulation of the Wnt pathway is of great importance. In this blog, we’ll focus on the key points about NOTUM and its role in regulating Wnt signaling.

NOTUM is a deacylase enzyme that has been shown to negatively regulate Wnt signaling by removing a lipid moiety (palmitoylation) from Wnt ligands. This deacylation process impairs the ability of Wnt ligands to bind to and activate their receptors on target cells, leading to a decrease in Wnt signaling activity. NOTUM is conserved in vertebrates, and its expression is tightly regulated during development and in adult tissues.

Recent studies have highlighted the importance of NOTUM in several biological processes, including embryonic development, tissue repair, and cancer progression. For example, NOTUM has been shown to regulate the formation of the anterior-posterior axis during embryonic development in zebrafish, where it modulates Wnt signaling activity in a tissue-specific manner. Moreover, NOTUM has been implicated in the regulation of tissue repair and regeneration by modulating Wnt signaling activity in stem cells.

In addition to its role in normal biology, NOTUM has also been shown to play a role in cancer progression. NOTUM expression is upregulated in several cancer types, including colorectal, pancreatic, and liver cancer. In these tumors, NOTUM expression is associated with poor prognosis and is thought to contribute to cancer progression by modulating Wnt signaling activity.

In conclusion, NOTUM is a deacylase enzyme that plays a critical role in regulating the Wnt signaling pathway. Its expression and activity are tightly regulated during development and in adult tissues, and dysregulation of NOTUM has been associated with several human diseases, including cancer. Understanding the regulation of NOTUM and its role in the Wnt signaling pathway may provide new insights into the development and progression of human diseases, including cancer.