Mitochondrial catalase induces cells transformation through nucleolin-dependent Cox-2 mRNA stabilization.

It's well documented that over-production of reactive oxygen species (ROS) causes detrimental damages to cells. While a low level of ROS, such as HO, functions as signaling transducer and motivates cell proliferation in both cancer and non-transformed stem cells. As a double-edged sword, the direct evidence for demonstrating the function of HO in the cause of tumor is barely characterized in intact cells. In our current study, we found that targeted expression of mitochondrial catalase (mCAT), but not catalase, could significantly reduce the accumulation of HO in mouse epithelial JB6 Cl41 cells, consequently led to the cell malignant transformation and anchorage-independent cell growth. Further study revealed that this reduction of HO resulted in the translocation of nucleolin from the cytoplasm to nuclear, and maintaining the nucleolin nuclear location status, and in turn stabilizing the cox-2 mRNA and consequently leading to a COX-2 protein upregulation, as well as malignant transforming mCAT-overexpressed Cl41 cells. Collectively, our studies here provide direct experimental evidence demonstrating a novel function and molecular mechanisms of mCAT in transforming mouse Cl41 cells, and high significance insight into understanding the beneficial aspect of HO in circumventing tumor promotion and the theoretical basis for the management of HO in the clinic implementation as a chemotherapeutic strategy.