The compression of certain cells can go so far as compromising nuclear envelope integrity by rupturing the nucleus, leading to DNA damage which then promotes the invasion of the destructive TREX1 enzyme. This enzyme is believed to cause tumorous cells to proliferate.
TREX1 Makes Breast Tumors More Invasive. Image Courtesy of Philippe Chavrier
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Damaged DNA
As the cells multiply and migrate, they can shrink and their nuclei break down. This phenomenon causes damage to their DNA, and researchers at the CNRS, Institut Curie, and Inserm have just shown that it promotes the proliferation of breast tumoral cells. The results of the study were published on 21 September in the journal Cell.
The cell wall plays an important role: it protects DNA and allows it to be used properly. However, it can become deformed or even temporarily broken when the cell itself is compressed and deformed, for example during migration or proliferation. The subsequent compression causes DNA damage. This leads to accelerated aging of healthy cells and the development of invasive properties by breast tumor cells, as has just been demonstrated by a research team from CNRS, Institut Curie, and Inserm.
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Does the TREX1 enzyme affect cancer progression?
Researchers have shown that breaks in the nucleus caused by cell compression allow DNA to come into contact with the destructive enzyme TREX1. Its job is normally to protect the cell by destroying the DNA of any viruses that might try to attack them, but in these unusual circumstances, it attacks the cell’s own DNA.
In healthy tissue, cells show signs of senescence and stop dividing. However, the research team found that the consequences are different in breast tumors: instead of killing cancer cells, the damage caused by TREX1 makes them more invasive.
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When a tumor grows too large, the cells become compressed and gain the ability to destroy their environment and invade neighboring tissues, increasing the risk of metastasis.
These results show the importance of the TREX1 enzyme in breast cancer development and also in aging. Researchers now want to identify and test molecules that could inhibit its function. Since TREX1 plays an important role in regulating inflammation and immunity, these inhibitors could have many therapeutic applications.
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References
Compromised nuclear envelope integrity drives TREX1-dependent DNA damage and tumor cell invasion
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