Mitochondria Clustering Helps Kill Cancer Cells

Scientists in Japan have discovered that cancer cell invasiveness can be inhibited by mitochondria aggregation.

AsianScientist (Sep. 24, 2018) – A team of scientists in Japan has found that mitochondria aggregation at the center of cancer cells prevents cancer cell invasiveness and promotes reactive oxygen species (ROS)-induced cell death. Their findings are published in Nature Communications.

Mitochondria are known to relocate within the cellular cytoplasm when different types of cells—including cancer cells—migrate. For example, they gather at the tail end of white blood cells moving toward a foreign invader, and at the leading edge of invading cancer cells. Mitochondria are also key sources of ROS in cells.

High levels of ROS are toxic to cancer cells, hence some treatments, including ionizing radiation, increase the production of ROS within cancer cells, resulting in their death. But some cancer cells develop a tolerance to ROS and therefore become resistant to treatment.

In the present study, researchers at Hokkaido University, Japan, sought to identify the link between mitochondria movement, ROS production and cancer cell invasiveness. The team tagged a variety of molecules inside invasive breast cancer cells with fluorescent compounds to track mitochondrial movements and ROS production.

They found that a molecular pathway which facilitates the recycling of integrin—a molecule that cells use to attach to their environment—also facilitates the localization of mitochondria. Integrin accumulation leads to the formation of an adhesion complex at the cell membrane, which ultimately induces trafficking of mitochondria to the cell periphery.

When the researchers disrupted this pathway, they observed that mitochondria aggregated near the center of cancer cells, which reduced cancer cell invasiveness. During the experiment, the team also directly modified the mitochondrial distribution and found that mitochondrial aggregation by itself leads to the production of excessive ROS, resulting in cancer cell death.

“[Our experiments have revealed] a novel molecular link between cell movements and mitochondrial dynamics, which appears to be crucial for both the invasive activity and tolerance to ROS of highly invasive cancers. Our findings may also lead to novel strategies to improve the efficacy of ROS-mediated cancer therapies, such as ionizing radiation,” said the researchers.

The article can be found at: Onodera et al. (2018) Arf6-driven Cell Invasion Is Intrinsically Linked to Trak1-mediated Mitochondrial Anterograde Trafficking to Avoid Oxidative Catastrophe.


Source: Hokkaido University.
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