Cancer cells face a unique challenge when migrating through narrow tissue structures, such as during metastasis. The high mechanical pressure they experience can lead to a rupture of the nuclear envelope, potentially causing DNA damage and cell death. However, researchers at the University of Freiburg’s Cluster of Excellence CIBSS—Center for Integrative Biological Signaling Studies have discovered a fascinating protective mechanism that comes into play in these situations.
A recent study published in The EMBO Journal reveals that a fine scaffold of actin filaments quickly forms in the cell nucleus following a nuclear envelope rupture. Actin, a key protein in cell structure, is driven by proteins DIAPH1 and DIAPH3, as well as the DNA damage sensor protein ATR. This scaffold stabilizes the nucleus, preventing DNA leakage and ensuring the survival of the cell.
Lead researcher Prof. Dr. Robert Grosse from the Institute of Experimental and Clinical Pharmacology and Toxicology at the University of Freiburg explains, “This protective mechanism provides an explanation for why cancer cells do not die despite high mechanical stress but can continue their migration.”
In their study, researchers used a highly invasive cancer cell line and observed actin filament formation within seconds of a nuclear envelope rupture in narrow microchannels. By measuring the mechanical properties of the cell nucleus and understanding how signals are passed between proteins, the team uncovered the importance of the ATR-formin axis in triggering actin filament formation.
The significance of this research extends to potential therapeutic approaches for cancer treatment. By targeting the ATR-formin axis, researchers believe they could inhibit this protective mechanism, potentially preventing metastasis or treating diseases involving unstable cell nuclei.
The study, titled “Nuclear rupture in confined cell migration triggers nuclear actin polymerization to limit chromatin leakage,” provides valuable insights into the survival mechanisms of cancer cells under mechanical stress. Further research in this area could lead to innovative treatments for cancer and other diseases.
For more information, you can access the full study published in The EMBO Journal under DOI: 10.1038/s44318-025-00566-2. This groundbreaking research was conducted by the Albert Ludwigs University of Freiburg and offers promising avenues for future medical advancements.
