Under normal conditions, human cells follow an orderly process to divide. They first copy their genome, then separate the copies and distribute the genetic material into two daughter cells. However, cancer cells can temporarily double their number of chromosomes, a phenomenon that has been poorly understood until now.
Researchers from
Johns Hopkins Medicine have identified a molecular pathway in human cells, offering promising new perspectives in the fight against cancer. This discovery could help explain how cancer cells manage to duplicate their genome excessively without dividing.
When cells are exposed to stress, such as drugs or UV radiation, they can enter a dormant phase. This process, meant to prevent division of damaged cells, can sometimes fail. Some stressed cells may try to recopy their genome, increasing the risk of cancer.
The team led by Sergi Regot studied cells from mammary ducts and lung tissues, which divide rapidly, allowing detailed observation of the cell cycle. The researchers used fluorescent biosensors to tag cyclin-dependent kinases (CDKs), which are essential for regulating the cell cycle.
Researchers found that under stress, the activity of CDK4 and CDK6 enzymes decreased, followed by CDK2, leading to premature activation of the APC protein complex, which is normally active during mitosis. This disruption prompts some cells to exit their resting phase and recopy their genome without dividing.
Video of a cell going through a stage of the cell cycle, duplicating its genome twice without dividing. Bright spots appear in the cell nucleus, indicating where DNA is being replicated.
Credit: Sergi Regot lab, Johns Hopkins Medicine
These observations are crucial as they could guide the development of new therapies. By combining DNA-damaging agents with CDK inhibitors, it might be possible to induce abnormal genomic duplication in cancer cells, making treatments more effective. Additionally, blocking premature activation of the APC could prevent tumor progression.
Research continues to understand the precise mechanisms and test new drug combinations. Ongoing clinical trials may reveal promising approaches to prevent excessive genome duplication in cancer cells.