Rho GTPases are molecular switches that control the cytoskeleton. The spreading of cancer cells from one part of the body to another, called metastasis, is one of the main causes of cancer death.

To metastasise, tumour cells must move through tissues, cross tissue boundaries and survive at secondary sites, which requires cell motility, remodelling of cell-cell contacts, interactions with the extracellular matrix and outgrowth at the secondary tissue.

Rho GTPases control actomyosin contractility, adhesive forces, matrix degradation and pro-survival signalling – all necessary for cells to migrate, disseminate and survive efficiently.

In our lab we are studying how Rho GTPase signalling and cytoskeletal remodelling can control all these processes that are crucial for metastatic cells to succeed at growing in a distant tissue, with a focus on these processes in the context of breast cancer. 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.

The team is working on identifying molecular cues that will aid in tumour metastatic dissemination via the crosstalk between the cytoskeleton and the nucleus. Moreover, whether metastatic cells develop an (epigenetic) memory is a matter of active investigation in the lab. We have a particular focus on Rho-kinase (ROCK) and Myosin II, as we believe this axis is crucial for the regulation of many processes in metastatic cancer cells.

How cancer cells interact with the tumour microenvironment is crucial for tumour progression and dissemination. The team aims to understand how the cytoskeleton in cancer cells affects cancer cell-normal cell communication.

Using co-cultures and 3-Dimensional matrix imaging systems, the team analyses communication of cancer cells with endothelial cells, fibroblasts and/or immune cells. These approaches allow manipulation of the cytoskeleton of cancer cells to analyse host tissue responses, both within the matrix and within the non-cancerous cells.

We also aim to understand if this process will be aided by signals sensed by the cytoskeleton of cancer cells and transmitted to transcription factors and/or chromatin. We think this is very important as cancer cells are addicted to transcriptional rewiring.

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. The ultimate goal is to define if manipulating the cytoskeleton of cancer cells will lead to improved efficacy of therapeutic approaches in patients with metastatic disease, with a special focus on breast cancer metastasis.