Anti-apoptotic mechanisms that mediate ras oncogene-driven tumor growth

The cells lining many human organs (epithelial cells) form a single layer. Cells that detach from this layer die. Cancer cells are often derived from epithelial cells. To spread to other parts of the body cancer cells have to be able to survive outside of the epithelial layer. Our goal is to understand the mechanisms allowing them to survive. To this end, we are studying a protein called Ras, which is thought to contribute to the progression of many cancers. Genetic alterations in cancer cells make Ras active at all times and allow it to rescue detached cells from dying. We found that Ras can reduce levels of a cell death-inducing protein called Chk2 in cancer cells. Our goal is to establish whether this change allows Ras to rescue detached cancer cells from death. If successful, our work could lead to a new type of cancer therapy based on blocking the ability of cancer cells to survive outside of their original location and spread to other parts of the body.