Principal Investigator Robert Weinberg
The ability of cancer cells to invade and metastasize is determined by the genetic changes that these cells have undergone during the course of multi-step tumorigenesis. In addition, the microenvironment of the cancer cell is a strong determinant of whether or not it acquires the capabilities to invade and metastasize. Thus, during the course of primary tumor formation, the cells in a carcinoma will recruit a complex array of mesenchymal cells from the host that together form the tumor-associated stroma. Prominent among these are fibroblasts and myofibroblasts. As tumor progression proceeds, the stromal cells create a "reactive stroma" that releases a variety of signals that impinge on the carcinoma cells and induce changes in their phenotype. We have begun to examine the nature of the signals that are released by this stroma and serve to induce the epithelial-mesenchymal transition (EMT), a profound change in cell phenotype that causes immotile epithelial cells to acquire traits such as motility, invasiveness, and resistance to apoptosis. These signals serve to induce expression of a series of transcription factors that are capable, in turn of inducing the EMT. A significant amount of our research is focused on the nature of these heterotypic signals and how they act, in concert, to induce expression of the EMT-inducing transcription factors in nearby carcinoma cells.