Novel Functions Of Stanniocalcin-1(STC1) Through Uncoupling Protein 2 (UCP2) Up-Regulation; Promoting Survival Of Cancer Cells Under Oxidative Stress And Inducing The Uncoupling Respiration (Warburg Effect)

We have demonstrated that multipotent stromal cells (MSCs) promote cell survival though upregulation and secretion of stanniocalcin-1 (STC1) (Stem Cells 2009; 27: 670-81). This study demonstrates that MSC derived STC1 promotes survival of lung cancer A549 cells through the uncoupling of oxidative phosphorylation, the reduction of intracellular reactive oxygen species (ROS) and concomitant shift towards a more glycolytic and more oxygen consumptive metabolic profile (known as the Uncoupling Respiration). MSC-derived STC1 upregulated uncoupling protein 2 (UCP2) in injured A549s in an STC1 dependent manner. Knock down of UCP2 reduced the ability of MSCs to reduce cell death in the A549 population. Our data suggest that MSCs promote cell survival by regulating the uncoupling respiration in an STC1 dependent manner. Furthermore, STC1 may provide promising avenues for treatment of reactive oxygen species and metabolic disorders.