Scientists just found cancer cells’ hidden power source

The discovery helps explain how cancer cells endure the harsh physical challenges they face as they migrate through dense tumors, squeeze into tiny blood vessels, and withstand the turbulence of the bloodstream. Understanding this energy mechanism could lead to new strategies for stopping cancer cells from spreading.

Mitochondria Rush to Rescue the Nucleus

Scientists at the Centre for Genomic Regulation (CRG) in Barcelona made the finding using a specialized microscope that can compress living cells to just three microns -- about one-thirtieth the width of a human hair. Within seconds of compression, mitochondria inside HeLa cancer cells were seen racing toward the cell nucleus and flooding it with extra ATP, the molecule that fuels cellular energy.

"It forces us to rethink the role of mitochondria in the human body. They aren't these static batteries powering our cells, but more like agile first responders that can be summoned in emergency situations when cells are literally pressed to the limit," says Dr. Sara Sdelci, co-corresponding author of the study.

Discovery of "NAM" Energy Halos

The mitochondria formed a glowing ring so dense that it caused the nucleus to indent. This pattern appeared in 84 percent of confined HeLa cells, compared with almost none in cells left uncompressed. The researchers named these structures "NAMs," short for nucleus-associated mitochondria.

To understand their purpose, the team used a fluorescent sensor that lights up when ATP enters the nucleus. Within three seconds of compression, the signal increased by about 60 percent. "It's a clear sign the cells are adapting to the strain and rewiring their metabolism," explains Dr. Fabio Pezzano, co-first author.

Energy Boost Fuels DNA Repair

Follow-up experiments revealed why this energy jolt is critical. Physical pressure damages DNA by stretching and breaking its strands. Repairing these breaks requires ATP to untangle and access the damaged regions. Cells that received the extra ATP from the mitochondria repaired their DNA within hours, while those that did not stalled in growth and division.

To test whether this process happens in real tumors, the researchers analyzed breast tumor biopsies from 17 patients. NAM halos were seen in 5.4 percent of cell nuclei at the invasive tumor edges, compared with 1.8 percent deeper inside the tumor. "Seeing this signature in patient biopsies convinced us of the relevance beyond the lab bench," says Dr. Ritobrata (Rito) Ghose, co-first author.

Cellular Architecture Behind the Energy Halo

The researchers were also able to study the cellular engineering which makes the mitochondrial rush possible. Actin filaments, the same protein cables that let muscles flex, compound around the nucleus, while the endoplasmic reticulum throws a mesh-like net. The combined scaffold, the study shows, physically traps the NAMs in place, forming the halo-like structure. When the researchers treated cells with latrunculin A, a drug that dismantles actin, NAM formation collapsed and the ATP tide receded.

If metastatic cells depend on NAM-driven ATP surges, drugs that block the scaffold could make tumors less invasive without broadly poisoning mitochondria and sparing healthy tissues. "Mechanical stress responses are an underexplored vulnerability of cancer cells that can open new therapeutic avenues," says Dr. Verena Ruprecht, co-corresponding author of the study.

A Universal Cellular Defense Mechanism

While the study looked at cancer cells, the authors of the study stress the phenomenon is likely a universal phenomenon in biology. Immune cells squeezing through lymph nodes, neurons extending branches, and embryonic cells during morphogenesis all experience similar physical forces.

"Wherever cells are under pressure, a nuclear energy boost is likely safeguarding the integrity of the genome," concludes Dr. Sdelci. "It's a completely new layer of regulation in cell biology, marking a fundamental shift in our understanding of how cells survive intense periods of physical stress."