New Study Reveals Active Metabolism in Cell Nucleus, Shedding Light on Cancer Research
In a groundbreaking study published in Molecular Systems Biology, researchers from the Centre for Genomic Regulation (CRG) in Barcelona and the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences have discovered that the cell nucleus is metabolically active. This finding challenges the long-held belief that the nucleus is metabolically inert and has significant implications for cancer research.
The study reveals that when a cell’s nucleus is in a state of crisis, such as widespread DNA damage, it calls upon mitochondrial machinery to carry out urgent repairs and protect the integrity of the genome. Previously, it was thought that the nucleus imported all its metabolic needs from the cytoplasm.
Cancer cells often hijack metabolic processes for their uncontrolled growth. This new understanding of the nucleus’s metabolic activity opens new avenues for cancer research by providing insights into how cancer cells manipulate metabolic processes and offering potential strategies to overcome drug resistance.
The researchers induced DNA damage in human cell lines using a common chemotherapy drug called etoposide. Surprisingly, they observed the generation and accumulation of reactive oxygen species inside the nucleus as a response to the DNA damage. These reactive oxygen species are dangerous by-products that can damage DNA.
The study also identified the enzyme PRDX1 as a crucial player in the nucleus’s response to DNA damage. PRDX1, which is normally found in mitochondria, travels to the nucleus and scavenges reactive oxygen species to prevent further damage. Additionally, PRDX1 regulates the availability of aspartate, a raw material necessary for synthesizing nucleotides, the building blocks of DNA. This finding suggests that targeting PRDX1 and nucleotide synthesis processes could enhance the effectiveness of therapies that damage DNA in cancer cells.
The researchers recommend exploring new treatment strategies that combine etoposide with drugs that boost the generation of reactive oxygen species. Additionally, combining etoposide with inhibitors of nucleotide synthesis processes could prevent the repair of DNA damage and ensure that cancer cells self-destruct properly.
Dr. Sara Sdelci, the corresponding author of the study and Group Leader at the Centre for Genomic Regulation, emphasizes the significance of the findings: “Our study demonstrates that another type of metabolism exists in cells and is found in the nucleus. Where there’s smoke, there are metabolic enzymes at work.”
Dr. Joanna Loizou, corresponding author and Group Leader at the CeMM Research Center for Molecular Medicine and the Medical University of Vienna, highlights the value of data-driven approaches in uncovering new biological processes: “Our findings shed light on how targeting these two pathways in cancer might improve therapeutic outcomes for patients.”
This groundbreaking research provides a new perspective on the role of metabolism in the nucleus and offers promising avenues for the development of more effective cancer treatments. By understanding and targeting the metabolic processes within the nucleus, researchers may be able to overcome drug resistance and develop innovative therapies that can more effectively eradicate cancer cells.