Epithelial-mesenchymal transition and genetic instability in breast cancer.

The microenvironment around cells contains an abundance of information. This includes localized signals from adjacent cells and the surrounding extracellular matrix, as well as soluble molecules such as hormones and growth factors. Collectively, these signals constitute the tissue context, and the behavior of every cell is profoundly influenced by the specific combination of signals presented to it. Functionally normal cells respond to these signals by organizing into structures that serve the body, filtering the blood in the kidney, digesting and internalizing nutrients in the intestine, and producing milk in the breast.

Cancer cells react to their tissue context quite differently, by continuing to grow and proliferate when they should not, by ceasing their productive functions and taking on dangerous new properties, and by separating from the surrounding cells and disseminating to distant locations in the body. Most existing cancer therapies target the consequences of the tumor cell genetic mutations, but these are limited by the ability of the tumor cells to develop drug resistance.

We are working to identify microenvironmental signals that are most involved in the earliest stages of cancer development and to define methods to target these processes with the ultimate goal of prevention of cancer development.