Pleiotropic role of NOTUM in colorectal cancer

Colorectal cancer (CRC) is one of the most common malignancies worldwide and a leading cause of cancer-related deaths. The vast majority of CRCs harbour a mutation in tumour suppressor gene adenomatous polyposis coli (APC), resulting in the continuous activation of the Wnt pathway.1 The subsequent translocation of β-catenin to the nucleus induces Wnt target gene expression that is regulating many key cellular processes including differentiation, stem cell self-renewal and proliferation. Given the importance of the Wnt pathway in homeostatic regulation, this pathway is tightly controlled to avoid excess signalling and thereby promoting tissue overgrowth or tumour initiation. Therefore, Wnt activity induces a negative feedback loop that facilitates the expression of negative Wnt regulators, including the Notum gene encoding the extracellular palmitoleoyl-protein carboxylesterase protein.2 Notum was first discovered in the Drosophila model organism, where a screen for genes interacting with wingless (wg) signalling, a pathway conserved...
Source: Gut - Category: Gastroenterology Authors: Tags: Open access, Gut Commentary Source Type: research