Cancer Signalling: The Wnt Pathway

Tubulovillous Polyp of the Colon

We are multi-cellular animals, and as such, our cells need to communicate with each other, so they can act in a coordinated manner in response to the environment. The basis of this communication comes from a process known as cell signalling. Various signalling molecules surrounding the cellular environment can stimulate cells to grow and divide at the appropriate time. When these carefully regulated cellular processes go wrong, cancer happens.

✤ The Wnt Signalling Pathway (pronounced ‘wint’) is one of the most studied signalling pathways in molecular biology. Discovered over thirty years ago, it is also a pathway that is frequently disrupted in cancer, particularly colon cancer. What is this pathway and how does it work?

✤ In Wnt signalling, the key effector is a molecule known as beta catenin. Under normal circumstances (when Wnt signalling is not active) beta catenin is constantly made by the cell and constantly destroyed. A new molecule of beta catenin only lasts in the cell for about 5 minutes before it is destroyed. However when Wnt signalling is active, this destruction is halted, so that beta catenin accumulates within the cell. Once beta catenin levels reach a certain threshold, it moves into the nucleus, binds to DNA and activates other genes that go on to promote cell division.

✤ One of the most common mutations in colon cancer is a gene known as APC. APC is part of the protein complex that destroys beta catenin. When APC is mutated, beta catenin cannot be destroyed; it accumulates in the cell and causes uncontrolled cell growth. It’s like a car with no brakes. It can lead to the development of hundreds of polyps in the colon as illustrated by the picture above. Although benign at first, these polyps can turn cancerous if left untreated. Unsurprisingly, people who have mutant APC have a nearly 100% chance of developing colon cancer by the age of 40 years.

✤ What effect does beta catenin activation have on different cells in our body? What are the other components of the Wnt signalling pathway and are there other ways in which beta catenin levels can be regulated by the cell? Can we exploit our knowledge of this pathway to inhibit beta catenin, to develop therapies to treat colon cancer? These are all areas of ongoing research, and there are many exciting new developments in the field of Wnt signalling.

On Sunday March 23, I will be speaking to +Akinola Emmanuel and +shilpa keerthivasan about their recently published research looking at Wnt signalling in immune cells. Their results are fascinating! You can RSVP to watch it here, and the video will be available on YouTube after the event.

For a great essay on the history of Wnt signalling, check out this review from the EMBO Journal (open access)

If you want to know more details on the mechanism of Wnt signalling, here’s a good video: The Wnt pathway in a normal and in a tumour cell

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