Cell biologist Renée van Amerongen of the Swammerdam Institute for Life Sciences has been awarded a €500,000 grant from KWF Kankerbestrijding. Van Amerongen will use this grant to expand her research efforts on dissecting the role of Wnt signalling in breast cancer.
Cellular communication pathways are composed of complex and dynamic protein networks that are capable of transmitting information from the extracellular environment to the inside of the cell. This allows a cell to respond to specific signals by adjusting its behaviour, either by changing its shape and movement or its identity and function. These decisions are usually complex, requiring changes in multiple genes and proteins, but phenotypically robust: cells are rarely confused as to whether they should divide or differentiate, unless these molecular signalling pathways are disrupted. Indeed, uncontrolled proliferation and cancer arise when multiple signalling pathways run out of control.
The research efforts of Van Amerongen and her team are focused on one particular signalling pathway, the so-called Wnt (pronounced ‘wind’) pathway. Wnt signalling has been conserved during evolution and is essential for the development of all multicellular animals to establish polarity (e.g. front/back) and to grow different tissues with specialised functions. Previous work by Van Amerongen and many others in the field already demonstrated that Wnt signalling controls breast development during puberty and pregnancy. Yet for a long time it appeared as if the Wnt pathway was not affected in human breast cancer patients. However, in recent years it has become clear that Wnt signalling is probably deregulated via subtle alterations, that for a long time proved simply more difficult to detect than those in colorectal cancer.
In this new project, Van Amerongen plans to resolve the role of Wnt signalling in breast cancer by taking a dual approach: on the one hand she will study the direct impact of Wnt signalling on different cell types in the mammary epithelium, either alone or in collaboration with other mutations typically found in specific breast cancer subtypes. On the other hand, her team will also test if and how different breast cancer subtypes respond to Wnt-pathway inhibition. The challenging goal is to perform most of these experiments in so-called organoids: complex tissue structures cultured in 3D, which closely mimic the situation inside the human body. To achieve this, Van Amerongen and her team will collaborate with Dr Christina Scheel (Helmholtz Zentrum, Munich, Germany), Dr Jos Jonkers (Netherlands Cancer Institute, Amsterdam) and Dr Hans Clevers (Hubrecht Institute, Utrecht).