New Anticancer Therapies Are Expected to Be Developed Through Specific Molecular Pathways in Cancer Cells

Recently, in a research report published in the international magazine Nature Communications, scientists from Hokkaido University have discovered a special pathway by studying molecules involved in mitochondrial movement in highly invasive breast cancer cells. It may promote the dispersal of these energy-generating organelles (mitochondria) around the cells, thereby increasing the aggressiveness of cancer.   The researchers claimed that when the pathway is blocked, mitochondria will accumulate at the center of the cell and begin to overproduce, causing reactive oxygen species (ROS) to leak and become unstable oxygen-containing molecules. Being considered to enhance the aggressiveness of cancer, however, ROS will induce cancer cell death when it is overdose. It is well known that mitochondria will reposition in the cytoplasm when different types of cells move, such as, they will accumulate at the end of white blood cells that move to an invader or gather at the front end of invasive cancer cells. Integrins on the cell surface promote cancer invasiveness, but the researchers are not aware of the molecular mechanisms involved.   Therapies such as ionizing radiation can increase the production of ROS molecules inside cancer cells, thereby inducing anticancer effects, however, some tumor cells are resistant to ROS. Researchers want to learn the way mitochondria move in cancer cells, and the relationship between these patterns of movement, integrins, and ROS. They used fluorescent compounds to label multiple molecules in invasive breast cancer cells, afterward following the mitochondrial movement and ROS production, and then the researchers blocked the function of key molecules involved in cancer cell invasion.   The researchers found that a specific molecular pathway called Arf6-AMP1-PRKD2 could promote the re-use of integrin in cells, meanwhile, promoting mitochondrial localization. The accumulation of integrins can lead to the formation of adhesion complexes in the cell membrane, which ultimately induces the transfer of mitochondria to the periphery of the cells. Interfering with these molecular pathways promotes the aggregation of mitochondria and reduces the invasiveness of cancer cells. In the study process, the researchers found that the mitochondrial self-aggregation may lead to excessive ROS production, thereby leading to cancer cell death through direct modification of the mitochondrial distribution.   The results of this study suggest that this pathway that facilitates mitochondrial diffusion may allow cancer cells to develop a degree of tolerance to therapies that attempt to kill cells by increasing reactive oxygen species. According to the researchers, this study reveals a molecular association between cell motility and dynamic changes in mitochondria, which appears to be critical for invasive activity of highly aggressive cancer cells and tolerance to reactive oxygen species. The results of this study are expected to help researchers develop new strategies to improve the therapeutic effects of reactive oxygen species-mediated cancer therapies, such as ionizing radiation therapy.