Johns Hopkins Medicine scientists have identified a molecular pathway that can lead cells down a dangerous path of duplicating their genome too many times, a characteristic of cancer cells. This pathway involves a group of molecules and enzymes that trigger and regulate the cell cycle, which is the process of making new cells from genetic material. The researchers suggest that therapies could be developed to interrupt these processes and potentially halt cancer growth.
Cells typically follow a routine of replicating their genome, separating the copies, and dividing the replicated DNA into two daughter cells. Healthy human cells have 46 chromosomes, but cancer cells can go through an intermediate state with 92 chromosomes. Researchers sought to understand how this happens and discovered that stressed cells can mistakenly copy their genome again, leading to potential cancer development. This challenges existing knowledge of the cell cycle and suggests a reevaluation of how it is regulated.
The researchers focused on human breast and lung cells, as they divide at a faster rate and provide more opportunities to observe the cell cycle. By imaging individual cells and using glowing biosensors to tag specific enzymes involved in the process, the team identified changes in CDK activity after exposure to stressors like UV radiation or osmotic stress. Decreased CDK activity was followed by the activation of the anaphase promoting complex before mitosis, indicating abnormal cell division.
When exposed to environmental stressors, about 90% of breast and lung cells enter a dormant state, but a small percentage continues to divide. The researchers linked an increase in stress-activated protein kinases to this small group of cells that replicate their genome twice. Clinical trials are underway to test drugs that block CDK activity, potentially leading to an increase in genome duplication and drug resistance in cancer cells. The researchers suggest that targeting the APC activation before mitosis may prevent cancer cells from replicating their genome twice and advancing to tumorous stages.
The study involved the collaboration of several researchers from Johns Hopkins, and funding was provided by the National Institutes of Health, National Science Foundation, and American Cancer Society. The findings contribute to a deeper understanding of the cell cycle and how it can go awry in cancer cells. By identifying the molecular pathways involved in genome duplication, researchers hope to develop targeted therapies to disrupt these processes and potentially stop cancer growth. Further research is needed to explore the potential of using drug combinations to prevent genome duplication and tumor progression in cancer cells.