In living organs, cells are in intimate contact with each other and with their microenvironment. In this context, cells display remarkable, and yet mysterious, “social” behaviors. Prominent examples are the ability of cells to stop proliferating (i.e. of making copies of themselves) in response to signals emanating from their surroundings or to change their behavior in response to tissue needs, as it occurs during wound healing. Healthy tissues can also recognize individual tumor cells, and either eliminate them, or induce them to "normalize" their behavior, as such taming the effect of oncogenic mutations.
These control systems are poorly understood because they represent forms of regulation that are proper of a cellular ensemble in its entirety. Thus, new experimental tools and conceptual paradigms are essential to understand the molecular basis of these tissue-level attributes. Addressing these unknowns has been a main focus of our ERC grant. We believe that understanding how cell communicate with each other and their environment will reveal a “treasure throve” of therapeutic opportunities in regenerative medicine and cancer treatment. This includes new ways to generate stem cells when the natural pool of these cells has been eroded by damage or ageing, and innovative strategies to prevent tumor emergence based on the body own healing capacities.
Our core objective has been to tackle the core question behind these biological events, that is, how normal cells change their fate once the environment is changing. In asking this, our primary perspective has been rooted to the notion that cells are embedded in mechanical signals emanating from their physical touching each other and the extracellular matrix to which they adhere. These signals are potent determinant of cell behavior affecting cells every second of their life. Cells respond to mechanical signals using special mechanosensory proteins, that are the YAP and TAZ transcription factors.
Through this ERC grant, our work revealed a striking overlap between stemness, tissue regeneration and cancer, all sharing features of cell fate plasticity dictated by the activation of YAP/TAZ transcriptional responses. Our insights in cancer biology and cell-cell communication have also with far-reaching implications in the biology of ageing and other human disorders.
