Cancer cell invasion and metastasis remain the leading cause of cancer-associated death. It is now clear that invasion is not simply a cancer cell autonomous process but the result of complex interaction between tumour cells and their microenvironment. A number of studies have now shown that the presence of Cancer Associated Fibroblasts (CAFs) in the tumour microenvironment enhance cancer cell invasion within the surrounding tissue, thus highlighting the interaction between CAFs and cancer cells as a promising therapeutic target to counteract cancer progression. Recent evidence has established that CAFs are able to guide the collective migration of cancer cells. While the ability of CAFs to rearrange the matrix and favour invasion is well established, how CAFs guide the forward motion of cancer cells remains unknown. To decipher the biophysical features of this cellular interaction we propose here a multidisciplinary project to study the physical forces that drive fibroblast-led collective cancer cell migration. To achieve this goal, we will use novel techniques developed at the host laboratory to measure the physical forces that cells exert on each other and on their surrounding matrix. Next, we will combine these force measurements with genetic and biochemical interventions targeting the interaction between CAFs and cancer cells. As the collective movement of cancer cells into tumor microenvironment is the first step in the spread of metastatic cancer, deciphering the interplay between mechanics and biology at the CAF-cancer cell interface will bring crucial insight into metastatic processes and potentially new therapeutic targets.
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