Francesco Baschieri, Gustave Roussy Institute, Villejuif, France

CAF-tracks support durotaxis of colorectal cancer cells

Recent advances in biophysics have underscored the importance of physical alterations of the tumor microenvironment in promoting metastatic dissemination. More specifically, it was observed in vivo that rigidity gradients participate in the process of cell dissemination in colorectal cancer. In vitro, fibroblasts have the capacity to do durotaxis, meaning to follow rigidity gradients going towards stiffer regions. However, cancer cells have lost this ability. I noticed that CAFs (cancer associated fibroblasts) do not only durotax, but also transmit durotactic information to cancer cells, thereby rendering them again sensitive to rigidity gradients. CAFs possess adhesive structures enriched in integrins and clathrin and when they move on stiff substrates, they leave such structures behind generating CAF-tracks that can be directionally followed by cancer cells. Aim of my research will be to selectively inhibit such structures only on CAFs to eliminate CAF-tracks responsible of durotaxis transfer to cancer cells. Concomitantly, I will study how cancer cells recognize CAF-tracks. This is most likely mediated by plasma membrane receptors, so I will analyze CAF-tracks by mass spectrometry to identify putative receptor-ligands that could represent new targets to tackle metastatic dissemination.