Introduction: A surprising energy boost under pressure
Scientists have uncovered a surprising mechanism that helps cancer cells survive the brutal mechanical gauntlets they must run to spread through the body. When cancer cells squeeze through dense tumor matrices, pores in blood vessels, and the bloodstream itself, they encounter intense physical stress. A team at the Centre for Genomic Regulation (CRG) in Barcelona observed that, within seconds of being compressed to three microns wide, mitochondria surge to the nucleus and pump in extra ATP, the energy currency of the cell. This rapid, local energy boost may enable cancer cells to endure migration and repair DNA damage that occurs during invasion.
How the NAMs power the cell under stress
Using a specialized microscope capable of compressing living cells, researchers watched 84 percent of confined HeLa cancer cells form a tight halo of mitochondria around the nucleus, a structure they dubbed NAMs — nucleus-associated mitochondria. In contrast, floating, uncompressed cells showed almost no NAM formation. The mitochondria appear to act as agile first responders, delivering ATP precisely where it is needed during mechanical stress, rather than serving as static energy reservoirs.
A fluorescent sensor confirmed the functional relevance: ATP entering the nucleus spiked by about 60 percent within three seconds of squeezing. “It’s a clear sign the cells are adapting to the strain and rewiring their metabolism,” notes Dr. Fabio Pezzano, co-first author of the study. This rapid metabolic reprogramming supports the idea that cancer cells can summon energy in the most demanding moments.
Why NAMs matter for DNA repair and survival
Mechanical squeezing can stress DNA, causing breaks and tangled strands. DNA repair requires ATP, and cells that receive this ATP surge repair damage more quickly, allowing continued division and potential metastatic spread. In experiments, squeezed cells that received extra ATP managed to repair DNA within hours, whereas those without the boost struggled to divide properly. This link between NAM-driven energy and DNA repair machinery highlights a vulnerability that could be exploited therapeutically.
Evidence from patient samples strengthens relevance
To test real-world significance, researchers examined breast-tumor biopsies from 17 patients. The NAM halo appeared in 5.4 percent of nuclei at invasive tumor fronts versus 1.8 percent in dense tumor cores, a roughly three-fold difference. Dr. Ritobrata Ghose emphasizes that finding NAM signatures in patient tissue supports the lab findings and suggests NAMs play a role in aggressive cancer behavior, not just in cell culture.
Mechanics of NAM formation: the cytoskeletal framework
The team traced how NAMs form. Actin filaments encircle the nucleus, while the endoplasmic reticulum forms a surrounding mesh, together constraining NAMs in place. When actin was disrupted with latrunculin A, NAMs collapsed and the ATP tide receded, underscoring the importance of this cytoskeletal scaffold in enabling the energy boost.
Implications for therapy and broader biology
If metastatic cancer cells rely on NAM-driven ATP surges, therapies that disrupt the NAM scaffold could reduce invasiveness without globally poisoning mitochondria and harming healthy tissue. “Mechanical stress responses are an underexplored vulnerability of cancer cells that can open new therapeutic avenues,” says Dr. Verena Ruprecht. Beyond cancer, the authors note NAMs could be a general feature of biology, as immune cells migrating through lymph nodes, neurons extending processes, and developing embryos all experience compressive forces.
A new layer in cellular regulation
Lead researcher Dr. Sara Sdelci reflects on the significance: NAMs suggest a new layer of regulation in cell biology, where energy supply is locally tuned in response to physical stress. The finding recontextualizes mitochondria not as stationary power plants but as adaptable responders vital to genome integrity during challenging conditions. As the research progresses, NAMs might become a focal point for therapies aimed at making cancer cells less resilient to mechanical challenges without harming normal cells.
Author insights
The study’s insights provide a compelling narrative: cancer cells, in their quest to spread, harness a rapid, nucleus-focused energy surge that supports DNA repair and survival when they are most vulnerable. By targeting the structural scaffold that enables NAM formation, researchers hope to blunt metastatic potential and improve outcomes for patients facing aggressive tumors.
