How Cancer Metastasis Happens: Researchers Reveal a Key Mechanism

Source: Weill Cornell Medical College

Summary: According to a new study researchers revealed that cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells.

How metastasis occurs has been one of the central mysteries of cancer biologyMetastasis is the term used for the spread of cancer to different parts of the body from where it originated. Chromosomal instability is a distinguishing characteristic of cancer that results from errors in chromosome segregation during a cell division. Until now the role of chromosomal instability in metastasis has not been clearly established. A new study by the researchers from Weill Cornell Medical College revealed that cancer metastasis can be triggered by a chronic DNA leakage within tumor cells. The authors traced the complex chain of events that result from chromosomal instability – a widespread feature of cancer cells in which DNA is copied incorrectly every time these cells divide, resulting in daughter cells with unequal DNA content. The study findings were published in the journal Nature.

Spread of cancer to different parts of the body from where it originated.

DNA (green) residing in fluid outside of cells’ main nuclei. Credit: Wenjing Wu/Memorial Sloan Kettering Cancer Center/Nature

Researchers injected chromosomally unstable tumor cells into mice and found that they were many times more likely to spread and form new tumors than tumor cells in which chromosomal instability was suppressed. On examination of the gene activity in the two sets of tumor cells, they also found that those with high chromosomal instability had abnormally elevated activity stemming from more than 1,500 genes – particularly in ones involved in inflammation and the response of the immune system to viral infections. Chromosomally unstable tumor cells, with their cytosolic DNA, are basically full of their own poison. Undoing their ability to suppress normal and lethal antiviral response to cytosolic DNA would, in principle, kill these aggressive cancer cells swiftly, with minimal effects on other cells.

Lead author Dr. Samuel Bakhoum said, “We showed that chromosomal instability can cause a leakage of DNA from the nuclei of cancer cells, leading to a chronic inflammatory response within the cells—and the cells essentially can hijack that response to enable themselves to spread to distant organs.

More Information: Samuel F. Bakhoum et al, “Chromosomal instability drives metastasis through a cytosolic DNA response”, Nature (2018). DOI: 10.1038/nature25432

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