Mitochondrion: A novel center for cancer cell signaling

Genomic alterations of normal host cells contribute to the development of cancer. Recent cancer research studies have shown that the aggressive growth and metastasis of cancer cells depend on normal host cells such as fibroblasts, endothelial, mesenchymal and immune cells. Balance among this cellular crosstalk determines the natural history of the cancer and its response to therapy. This active tumor-host dynamic mutualism is referred to as a tumor microenvironment, which can be a key target for both cancer prevention and therapy. An important common feature of various host cells and cancer cells is the generation of reactive oxygen species (ROS) that contribute to the effect of the microenvironment. Mitochondria play a central role in the regulation of ROS production and removal. A shift in cell redox status toward an oxidizing condition activates mitochondrial retrograde signaling, a communication pathway from mitochondria to the nucleus that leads to activation of adaptive response or cell death. Thus, in addition to generating ATP, mitochondria, the powerhouse of cells, play an important role in cell signaling in life-and-death conditions.