Mitochondrial linkage of Cancer

It has long been considered that the glycolysis is the major metabolic process that drives aberrant cancer cell proliferation, suggesting that the impaired mitochondrial function may be the underlying cause of cancer. These findings have eventually eradicated the major misconception that cancer is a purely cell-intrinsic disorder that stems from epigenetic or genetic alterations. Although the mitochondrial defect for cancer invasiveness is long known, its relation to treatment resistance remained unclear.

Recently, from the studies of aggressive breast cancer cells, scientists have found that the movement of mitochondria inside the cell is being controlled by the pathway- called Arf6-AMP1-PRKD2. It is known that the mitochondria generally move inside the cells under various circumstances but in cancer cells, it congregates in the leading rim of the cell. It is due to the pathway- Arf6-AMP1-PRKD2, which helps to recycle the protein, named integrin in the cancerous cells which then forms the adhesion complex in the cell’s membrane triggering the movement of mitochondria to the edge of the cell.

To understand the motion of the mitochondria in the cells, the researchers carried out the experiments in the breast cancer cells where they blocked the pathway. They observed that instead of the edge of the cell, the mitochondria congregate in the middle of the cell and thus, reduced invasiveness. This happens because the mitochondria started to produce and release excessive amounts of unstable oxygen-rich molecules known as reactive oxygen species (ROS) in the middle of the cell. The ROS molecules promote cancer invasiveness up to certain levels but when they become in excess, they kill cancer cells.

Radiotherapy uses ionizing radiation to shrink or eradicate tumors by increasing the production of ROS molecule inside the cancer cells. However, some cancers have become resistant to radiotherapy and other treatments that employ the ROS molecules as they have developed the tolerance to the molecules. But these findings of the molecular link between cell movements and mitochondrial dynamics may lead to novel strategies to improve ROS-mediated cancer therapies.