About Us
Our lab is focused on understanding the role of extracellular matrix (ECM) internalisation in cancer. The ECM is a complex network of secreted proteins, such as collagens, laminins and fibronectin, which, besides providing support for tissues and organs, also plays an active role in controlling a variety of cellular processes, including cell migration, proliferation and oncogenic transformation.
Our Research
We recently demonstrated that the internalisation of ECM components is strongly up-regulated in invasive cancer cells, compared to normal epithelial cells and non-invasive cancer cells. We developed a high-throughput screen to identify novel regulators of ECM uptake and found that the a2b1 integrin and p38/MAPK axis is required for this process and for breast, pancreatic and ovarian cancer cell invasive migration (Martinez et al, 2024). Furthermore, we found that ECM endocytosis sustains cancer cell growth in nutrient-deprived conditions, indicating that the ECM could represent a source of food for starved cancer cells (Nazemi et al., 2024).
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In a separate project, we found that the small GTPase RAB25 promoted the expression of the protease ADAMTS5 in ovarian cancer cells, in an NFkB-dependent manner. Importantly, secreted ADAMTS5 was necessary and sufficient to drive cell migration and invasion in 2D and 3D systems (Yuan et al., 2025).
We are currently addressing 3 main research questions:
How is ECM internalisation regulated? We are investigating the role of several hits from our screen fo the identification of novel regulators of ECM uptake (including actin dynamics and phosphoinositide signalling). In addition, we are exploring the contribution of extracellular ECM degradation by protease to ECM endocytosis.
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How does the RAB25/ADAMTS5 axis promote
peritoneal metastasis in ovarian and pancreatic
cancer? We use an in vitro co-culture model to
recapitulate the early metastasis stages, as well as a
Zebrafish in vivo cancer model
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How does the ECM influence therapy response? We are investigating how the presence of
ECM impacts on cancer cell responses to commonly used chemotherapy drugs, both in ovarian and pancreatic cancer cells
Our Funders
We would like to thank the following organisation for supporting our work
