Seventh Framework Programme - European Union
An EU consortium to identify novel targets and drugs for cancer treatment

Signs and signals:
Signal activity

By Brona McVittie

“One of the signaling pathways we’re particularly interested in is called Wnt., says Michael Boutros. “The pathway operates inside the cells of most organisms from worms to man, so we’ve learned a lot from flies. Signaling pathways usually regulate the processes of growth and cell specialisation but they can lead to over-proliferation of cells when messed up.”

“For example Wnt signaling, when over-activated, leads to colorectal cancer. In the colon a lot of cells are constantly shed and replaced. Certain types of stem cells replenish the lining of the colon. Wnt activity in this tissue is high because it helps to regulate the process of making new cells. However, mutations in Wnt components can occur causing the pathway to over-activate, which leads to colon cancer.”

“A mutated Wnt component can alter the activity of the pathway. In principle, we could target the mutated component or other components that act subsequently in the pathway with a drug. However a lot of these signaling pathways interweave, which is important if you want to design a drug against a signaling factor that is part of two or three different signaling routes. Unwanted side effects could result for this reason. We don’t know much about that yet”.

“We’re still surprised about how much we don’t know, because we find many things that previous genomic screens have not described. In one of the RNAi screens we did, we found a component that is specifically required for Wnt proteins to leave the cell, but it’s not required for the exit of any other protein.”

Signaling pathways keep fundamental processes in order during development. They have different roles in different tissues, so when they go awry the effects are unpredictable. For this reason, they are implicated in many different diseases. For example, Wnt signaling plays a role not only in the onset of colon cancer, but breast cancers and cancers of the nervous system.