Since the very early days of cell biology studies, more than 100 years ago, researchers recognized the importance of cell attachment to rigid surfaces and its essential role in growth and migration. Later it was recognized that unlike normal tissue cells, cancer cells are able to grow in suspension without solid support, making them “anchorage‐independent”. This hallmark property of cancer cells has highlighted the importance of correct sensing of the mechanical properties of the extracellular matrix (ECM). In particular, ECM rigidity has emerged as a major determinant of many cellular aspects – including survival, migration, proliferation, and differentiation.
Our lab aims to elucidate the mechanisms by which cells sense and respond to mechanical features of their environment. We combine advanced microscopy techniques with biophysical measurements to decipher the pathways by which extracellular mechanical signals are transmitted into biochemical signals inside the cells. We then study how these mechanosensing events are integrated in time and space to affect cellular behavior. We would like to understand how these processes are altered in cancer given the observation that proper mechanosensing is malfunctioning in cancer cells.
Our results show that there is a critical role for proper regulation of cellular forces. Under normal conditions, cells apply forces that are proportional to matrix rigidity (namely, higher rigidity = higher forces). However, cancer cells often down-regulate proteins that are important for controlling the proper force level, and thus the contractile units are disorganized and the forces that are produced are constantly high (regardless of matrix rigidity).
Our working model is that in adhesions that form at the cell edge for rigidity sensing there are mechanosensory proteins that change their conformations in response to force. This initiates the activation of signaling cascades that ultimately lead to changes in cell behavior. In cancer cells that display high forces constantly, the mechanosensors are hyper-activated regardless of rigidity and thus the cells can grow under anchorage-independent conditions.