Metastasis is responsible for ~90% of cancer patient deaths. In order for cancer cells to spread, they need to adapt to the tissue environment they encounter. On their journey they will meet obstacles of various physical properties (rigidity, confinement, adhesion and topology), and the cells have therefore developed strategies to circumvent these challenges, a term known as ‘plasticity of cell migration’. We recently discovered that the STRIPAK complex is an important and ancient regulator of ‘plasticity of cell migration’ in both developmental processes and cancer metastasis; we believe that we have discovered a novel developmental mechanism hijacked by the tumour cells.
We will use high resolution imaging and intravital imaging to understand how the STRIPAK complex is regulating cancer cell migration through tissue. We will also substantiate the prognostic values of perturbed and mutated STRIPAK component in cancer patients. The aim is to push this discovery, and to determine if this can be turned into a prognostic test that might inform how aggressively the cancer disease should be treated.
Activation of cancer-associated fibroblasts (CAFs) is another detrimental regulator of the environment. CAFs promote cancer progression and cancer cell dissemination. We have only just discovered that CAF activation can be reverted towards a quiescence state. We will attempt to determine the epigenetic changes and the coexisting mechanisms taking place in CAFs during cancer evolution.