"Energy bursts" released by cancer cells may pave the way for new therapeutic policies.

 

Cancer

"Energy bursts" released by cancer cells may pave the way for new therapeutic policies.

A team of researchers in Spain has made a new scientific discovery that may pave the way for new therapeutic strategies to eradicate cancer. Scientists at the Center for Genome Regulation in Barcelona found that cancer cells release bursts of energy when exposed to stress within the body. Mitochondria, the energy-producing units of living cells, move toward the nucleus of the cancer cell, releasing additional energy that helps repair damage to the cell's DNA and protect it from excessive external stress.

The study, published in the scientific journal Nature Communications, confirmed that laboratory tests on samples of tumors removed from patients revealed that cancer cells double their energy production when exposed to stress. This could explain the mechanisms malignant cells use to survive within the body, such as creeping within tumors, infiltrating arterial pores, or withstanding pressure forces within the bloodstream.

For this study, Spanish researchers used a specialized microscope that can compress a living cell to a width of no more than 3 microns, equivalent to one-thirteenth the diameter of a human hair. They observed that within seconds of the compression process, mitochondria move toward the surface of the cell nucleus and release bursts of adenosine triphosphate (ATP), the energy currency at the molecular level within a living cell.

In statements to the scientific research website "Science Daily", researcher Sarah Sedileshi from the Center for Genome Regulation and one of the study's co-authors said that the way mitochondria move towards the surface of the nucleus inside a "besieged" cancer cell makes us rethink the role of these units within a living human cell. They are not just static batteries that supply the cell with energy, but rather they respond when called upon to confront emergency situations, such as when the cell is exposed to external stresses that exceed its ability to withstand.

The researchers found that mitochondria cluster so tightly on the surface of the cell nucleus that the nucleus compresses inward. They observed this phenomenon in 84% of cases of cancer cells exposed to stress, compared to cases of cancer cells moving normally without stress. The researchers named these structures "nucleus-associated mitochondria."

To verify this hypothesis, the researchers used fluorescent sensors that emit light flashes when the adenosine triphosphate molecules referred to above bind to the cell nucleus. They observed a nearly 60% increase in flashes within just three seconds of the cancer cell beginning to compress.

These flashes are "a clear indication that cells are adapting to stress and reshaping their metabolism as a result," says study co-author Dr. Fabio Pisano. Subsequent experiments have demonstrated the importance of rapid energy bursts for the survival of cancer cells, as mechanical compression of the cell leads to DNA strands breaking under external stress and entanglement of the genome within the nucleus.

Cells rely on "repair teams" within the cell to reach damaged sections of DNA to repair them, but these teams are hungry for energy in the form of ATP. So if compressed cancer cells get the necessary energy bursts, they can repair the damage within hours. Without those bursts, they stop dividing and growing normally.

The researchers were also able to identify the cellular engineering mechanism that allows mitochondria to fuse to the cell nucleus when subjected to stress. They observed that a network of actin filaments—the same type of protein filaments that allow muscles to contract inside the body—forms around the nucleus, and that this network secures the mitochondria in their correct position around the nucleus.

When the researchers injected these cells with latrunsulin, a substance that dissolves actin, the mitochondrial formations around the nucleus collapsed, and the energy flows that fuel the cancer cells were reduced. Based on this experiment, the researchers believe that if cancer metastases rely on energy flows from clusters of mitochondria around the nucleus to invade the body, then using drugs that dissolve actin networks without poisoning the mitochondria themselves could prevent the spread of cancer to healthy tissue."The mechanical response to stress within cancer cells is one of the weak points of cancer that has not been widely addressed by science, and it could open the door to new therapeutic avenues," says Dr. Verena Rupprecht, a member of the study team.

The study team emphasizes that although this research focuses on the effect of compression on cancer cells, the response of living cells in general to pressure is a common phenomenon in biology. Science has been able to observe the compression of immune cells within lymph nodes and the compression of embryonic cells during embryonic development in the womb.

"Whenever a living cell is stressed by external factors, it releases bursts of energy to maintain the integrity of its genome," says Dr. Sedlci. "Studying this phenomenon could radically change our understanding of how living cells generally survive when exposed to mechanical stress."