Academy of Finland awarded Guillaume Jacquemet (Ivaska lab) with Academy Postdoctoral Fellow funding 259 054 € for 2017-2020

Myo10 filopodia and cancer metastasis
The formation of metastases is responsible for 90% of deaths in patients with solid tumours. Consequently, there is a pressing need to develop therapeutic strategies that block the ability of cancer cell to disseminate throughout the body. We and others have made an intriguing discovery that cancer metastasis is associated with the development of specialized cellular protrusions called filopodia. In migrating cells, filopodia are “antenna-like” protrusions, which contain cell-surface adhesion receptors, such as integrins, responsible for constantly probing the cellular environment. At filopodia, integrins modulate signalling pathways that support cell migration, survival and proliferation. Integrins are transported to filopodia via a motor protein called Myosin-X, a regulator of filopodia formation. Based on our breakthrough experiments, we discovered that myosin-X contribute to cancer cell metastases in vitro and in vivo models and that myosin-X is highly expressed in patient samples (including breast, pancreatic, colorectal, glioma and lung carcinoma) where it correlates with poor prognosis. These results clearly indicate that myosin-X is a promising novel target for anti-cancer therapies. Data I accumulated to date clearly demonstrate that myosin-X-mediated transport of integrins, together with integrin signalling in filopodia are two important prerequisites for cancer metastasis. Therefore, I aim to develop strategies to target myosin-X in cancer by 1) generating myosin-X-specific small molecule inhibitors in collaboration with the non-profit organization CD3 (University of Leuven), 2) identifying the regulatory mechanisms by which myosin-X transports integrins to filopodia and 3) assessing the role of Myo10 filopodia in in vivo dissemination of cancer cells using intravital microscopy. If sucessful, our findings will lead to the development of a drug that can inhibit Myo10 function in cancer and thus provide novel and desperately needed therapeutic strategies for treating metastatic pancreatic and breast cancer as well as other cancer forms.