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Rho GTPases, the cytoskeleton and cancer metastasis

Rho GTPases are molecular switches that control the cytoskeleton. Deregulation of Rho GTPases can result in aberrant function and disease, including cancer. The spreading of cancer cells from one part of the body to another, called metastasis, is one of the biggest causes of cancer death. To metastasise, tumor cells must move through tissues and cross tissue boundaries, which requires cell motility, remodeling of cell-cell contacts and interactions with the extracellular matrix. Rho GTPases control actomyosin contractility, adhesive forces and matrix degradation, all necessary for cells to migrate and disseminate efficiently.

In our lab we are studying how Rho GTPase signalling and cytoskeletal remodelling can control many processes, including cell migration, invasion and metastasis. We are particularly interested in understanding how cancer cells sense extracellular signals via their cytoskeleton and integrate the responses altering gene transcription to promote metastasis.

​​​​​​​ Therefore, our group is working on identifying molecular cues that will aid in tumour metastatic dissemination via the crosstalk between the cytoskeleton and the nucleus. We have a particular focus on Rho-kinase (ROCK) and Myosin II, as we believe they are crucial for the regulation of many processes in cancer cells. We study the behaviour of very aggressive cancers such as melanoma, a cancer of the skin, in which we specialize. The lab is highly multidisciplinary, as we use a combination of “OMICs”, state of the art microscopy, molecular and cellular biology, animal models and patient material.

Tumour microenvironment

How cancer cells interact with the tumour microenvironment is crucial for tumour progression and dissemination. Therefore, we are very keen on understanding how the cytoskeleton in cancer cells affects cancer-stromal communication. We have developed co-cultures and 3-Dimensional matrix imaging systems to analyse communication of cancer cells, endothelial cells and immune cells.

These approaches allow us to manipulate the cytoskeleton of cancer cells, and then analyse stromal responses, both the matrix and the non-cancerous cells. We are particularly interested in understanding if the cytoskeleton of cancer cells will dictate specific tumour micro-environmental organization. We also aim to understand if this will be aided by signals sensed by the cytoskeleton of cancer cells and transmitted to nuclear transcription factors. We think this is very important as cancer cells are addicted to transcriptional rewiring.

**Our ultimate goal is to define if manipulations in the cytoskeleton of cancer cells will lead to improved efficacy of current therapeutic approaches in patients via transcriptional reprogramming.