Most cancers are driven by persistent cell division, and the cause is largely a mystery. Scientists at Vanderbilt University have discovered a genetic mutation that seems to be at odds with that extreme proliferation of cells – and they did it with the CRISPR gene expression system.
Using a CRISPR genomewide screen, the Vanderbilt team found that deletion of proteins produced by the TRAF3 gene causes cells to shrink non-stop, even after reaching a certain density that would normally indicate non-stop separate them. Since TRAF3 has not been linked to cancer before, the finding could provide key insights into the development of some cancers, the researchers reported in the journal eLife.
The team started with 40 million epithelial cells, using CRISPR to select cells that kept dividing uncontrollably. They were surprised to learn that the loss of activated TRAF3 indicates that that in turn drives cell proliferation. TRAF3 normally activates immunity and had not previously been linked to unregulated cell growth, they said.
“Normal, unregulated cells are known to determine when they stop dividing by sensing the density of the cells around them, but cancer cells do not have that restriction and just keep going. separating. It is important that we understand the mechanisms that control this type of cellular behavior, ”graduate student and lead author Maria Fomicheva said in a statement.
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Finding new ways to stop unregulated cell division in cancer is a growing interest in oncology research. In September last year, the Johns Hopkins team reported that they were able to stop breast cancer cells from proliferating by blocking the protein PLK4, which disrupted side structure. inside cells that are essential for division.
In 2018, a team of researchers found that inhibition of the enzyme DHODH could stop cells from dividing. A team at the University of Rochester used CRISPR to secrete the Tudor-SN protein from cells, which slowed down the process of cell division.
Since the Vanderbilt team discovered the role of TRAF3 in cell division using epithelial cells – immune cells that line the skin and internal organs – the finding could be particularly useful for understand cancers that start in epithelial tumors, such as gastric and lung cancers, the researchers wrote in the study.
TRAF3 mutations have been found in some epithelial cancers, they said, “and low mood is associated with worse outcomes. Further work is needed to determine the impact of this pathway in cancer development. “