Grant: Operating Grant

Controlled cell division, or proliferation, is essential for normal growth and function of the developing and adult organisms. Importantly, unchecked cell proliferation may cause increased number of cells, or tumors, that can turn into cancer. Controlling cell proliferation requires that cells communicate with each other by secreting different types of growth factors into the external side of these cells. Some of these growth factors instruct cells to proliferate, while others stop cells form dividing. The TGF-ßs are members of a family of secreted growth factors that prevent many normal cell types from proliferating. However, cells may change to become resistant to anti-proliferative effect of TGFß. This change can potentially start small tumors. At later stages of tumor development, TGF-ß can produce other effects on these cells, such as changes in cell shape and promotion of cell movement. These TGFß-effects may help the tumors to be metastatic because cancer cells can spread into the blood stream. Once blood bourn cancer cells can spread into other parts of the body. In general, cancer may arise from either an increase in the amount or activity of cellular factors that promote cell proliferation and enhance the ability of cells to migrate. These cellular factors are referred to as proto-oncogenes. Tumors can also result from a decrease in the amount or function of cellular factors that prevent cell proliferation and resist cell movement. These types of factors are called tumor suppressors. The overall goal of this research proposal is to understand which and how changes in proto-oncogenes or tumor suppressors affect the ability of cells to respond to TGF-ß. This work will increase our understanding of the causes of cancer and may lead to new therapeutic advances to combat this devastating disease.