Intracellular protein localization involved in new tumor progression pathway

Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis

As cancer progresses, cancer cells acquire the ability to become resistant to programmed-cell-death, called apoptosis. Understanding the molecular mechanisms involved in the regulation of apoptosis is key for developing proper cancer therapies. Survivin is a member of a family of proteins that are inhibitors of apoptosis (IAPs), but the means by which survivin inhibits apoptosis remains largely unknown. Dario Altieri and colleagues, from the University of Massachusetts Medical School, investigated the where survivin is located within the cell to see whether the cellular location is directly involved in the regulation of apoptosis and the establishment and progression of tumors.

The authors identified a specific mitochondrial pool of survivin that is released into the cytoplasm when a cell receives signals to undergo cell death. Once in the cytoplasm, survivin inhibits enzymes called caspases which are required for apoptosis, and in doing so, blocks apoptosis. The researchers showed that by selectively targeting survivin to the mitochondria this enhanced soft agar colony formation, which is a standard laboratory technique to test for cells that lack growth control and are potentially tumor forming. In mice, when the authors carried out such mitochondrial targeting of survivin, this resulted in increased tumor growth and eleimination of apoptosis. The data here demon-strate a novel pathway for apoptosis inhibition and tumor progression.