Scientists unveil a hidden power source inside cancer cells
In a breakthrough that could reshape how we understand cancer survival, researchers from the Centre for Genomic Regulation (CRG) in Barcelona have identified a rapid mitochondrial response inside squeezed cancer cells. When cancer cells endure the brutal mechanical gauntlets of moving through a tumor’s dense matrix or slipping into porous blood vessels, they seem to summon a powerful energy boost. This boost comes in the form of the mitochondria racing to the nucleus and pumping in ATP, the molecular fuel that powers cellular processes.
The NAMs: nucleus-associated mitochondria
Using a specialized microscope capable of compressing living cells to three microns wide, the team observed a remarkable reorganizing act within HeLa cells. Within seconds of compression, mitochondria form a halo around the nucleus, creating a dimple in the nucleus itself. The researchers named these structures NAMs, or nucleus-associated mitochondria. The effect was striking: NAM halos appeared in about 84 percent of confined cancer cells, compared with almost none in floating, uncompressed cells.
How NAMs respond to mechanical stress
To probe the function of NAMs, scientists deployed a fluorescent sensor that lights up when ATP enters the nucleus. When cells were squeezed, the sensor’s signal rose roughly 60 percent within three seconds. “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. The quick ATP surge indicates NAMs are not merely reactive; they are part of an emergency response that helps cancer cells cope with extreme physical stress.
Why this ATP surge matters for DNA repair and growth
Mechanical squeezing punctures DNA, snapping strands and tangling the genome. The cell’s repair machinery is ATP-hungry and must reach damaged sites to restore integrity. In experiments, squeezed cells that received an NAM-driven ATP boost were able to repair DNA within hours, while those lacking the surge failed to divide effectively. This connection between NAM activity and genome maintenance suggests the energy boost is a pivotal factor enabling cancer cells to survive and potentially spread under hostile conditions.
Evidence beyond the lab: relevance to patients
To test clinical significance, the team analyzed breast-tumor biopsies from 17 patients. NAM halos appeared in 5.4 percent of nuclei at invasive tumor fronts, compared with 1.8 percent in the dense tumor core—a three-fold difference. Dr. Ritobrata Ghose emphasizes that spotting this signature in patient samples validates the laboratory findings and points to a real-world mechanism by which cancer cells endure physical challenges during invasion.
The cellular framework that enables NAM formation
The study also explored how the NAM halo is assembled. Actin filaments—protein cables that power muscle contraction—surround the nucleus, while the endoplasmic reticulum forms a mesh-like net. Together, this scaffolding traps NAMs in place, creating the halo structure. When the team treated cells with latrunculin A, a drug that disrupts actin, NAM formation collapsed and the ATP surge receded. This demonstrates that the cytoskeletal framework is essential for NAM-mediated energy boosts.
Therapeutic implications: a new vulnerability in cancer
If metastatic cells rely on NAM-driven ATP surges to withstand mechanical stress, targeting the scaffolding that supports NAMs could dampen invasiveness. Such an approach would aim to disrupt the energy boost at its source without broadly poisoning mitochondria and harming 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.
A broader biological insight
Though the study centers on cancer cells, the authors suggest NAM-like mechanisms may be universal. Immune cells squeezing through lymph nodes, neurons extending branches, and embryonic cells during development all experience similar physical stresses. The research hints at a general principle: when cells are pressed to their limits, they may summon a nuclear ATP boost to protect genome integrity. Dr. Sara Sdelci frames NAMs as a “new layer of regulation in cell biology,” signaling a shift in how scientists understand cell survival under pressure.
Looking ahead
The discovery opens multiple avenues for future work—further characterizing NAM dynamics, identifying drugs that selectively disrupt the NAM scaffold, and exploring NAM activity across different cancer types and stages. As researchers push forward, the NAM mechanism could become a focal point for therapies designed to render tumors less capable of invasion while sparing normal cells.
