The findings could potentially lead to new therapies and could stop the growth of cancers
Johns Hopkins Medicine scientists have revealed a molecular pathway that lures cells down a path of genome duplication, a hallmark of cancer cells, which could potentially lead to new therapies and could stop the growth of cancers.
Published in Science, the study reveals the consequences of molecules and enzymes triggering and regulating the process of making new cells out of the cells’ genetic material.
Cells follow an orderly routine that begins with making a copy of their entire genome, followed by separating the genome copies and dividing the replicated DNA evenly into two “daughter” cells.
When doing so, cells that are stressed can mistakenly run the risk of copying their genome again.
Focusing on human cells that line breast ducts and lung tissue, scientists analysed thousands of images of single cells as they went through cell division and developed glowing biosensors to tag cyclin dependent kinases (CDKs), which play a key role in cell cycle regulation.
They found that a variety of CDKs were activated at different times during the cell cycle and, after exposure to an environmental stressor, researchers observed that CDK 4 and CDK 6 activity decreased.
Up to six hours later, when the cells were preparing to divide, CDK 2 was inhibited while a protein complex known as the anaphase-promoting complex (APC) was activated, just before mitosis, where the cell pulls apart and divides.
The research team observed that up to 10% of the breast and lung cells returned to the cell cycle, dividing their chromosomes again, suggesting that a combination of drugs could “spur some cancer cells to duplicate their genome twice and generate the heterogeneity that ultimately confers drug resistance,” explained Sergi Regot, associate professor, molecular biology and genetics, Johns Hopkins University School of Medicine.
He continued: “There may be drugs that can block APC from activating before mitosis to prevent cancer cells from replicating their genome twice and prevent tumour stage progression.”
