A gene known as CTNNB1 encodes for a crucial protein called β-catenin, which has an important role in controlling tissue repair and cell growth. If this gene and its protein are dysfunctional, it can lead to uncontrolled cell growth, which is the central feature of cancer. Scientists have now sought to understand how various mutations in CTNNB1 can affect cells, and how they can lead to cancer. This study, which was reported in Nature Genetics, could help scientists develop better cancer treatments for cancers that are related to mutations in CTNNB1.
There are many mutations in a certain region of CTNNB1 that have been associated with various types of cancer. When the gene is functioning normally, this region can tag β-catenin for elimination when the cell doesn’t need it anymore. But mutants can disrupt this tag and remove it, so the mutated β-catenin hangs around, and triggers the activity of genes in the so-called β-catenin pathway that can promote tumor growth
There are over 70 mutations in this part of CTNNB1 that have been found in various cancer types. In this work, the researchers tested the effects of 342 different mutations in this CTNNB1 hotspot in a mouse stem cell model, which have many things in common with human cells. The scientists determined how much each mutation activated the β-catenin pathway. Some mutations had mild or moderate effects while others had much more significant impacts.
These findings were compared to data collected from cancer patients, and the investigators found that the mutations that each patient carried was reflected in how β-catenin was impacted.
In liver cancer patients, for example, tumors tended to fall into one of two groups: one group had less serious CTNNB1 mutations, and there were more immune cells around these tumors; while in another group, the mutations had stronger effects, and there were fewer immune cells in the tumor microenvironment.
The strength of CTNNB1 mutations could be affecting the interaction between the tumor interacts with the immune system, and maybe the effect of immunotherapy. More research will be needed to determine if that’s true, however.
“The new map provides a powerful tool for predicting how specific CTNNB1 mutations affect cancer behavior and could support the development of more personalized treatments. As the first study to experimentally test every possible mutation in this critical hotspot, it gives scientists a clearer picture of how β-catenin drives tumor growth across different cancer types,” said Andrew Wood, a Principal Investigator at the University of Edinburgh’s Institute of Genetics and Cancer.
Sources: The University of Edinburgh, Nature Genetics
