基因突变,癌细胞 z-bo 2020-09-23 370

　　A new study reveals how gene mutations promote the growth of aggressive tumors in several human cancers, including leukemia, glioma, and melanoma.

　　Scripps Research associate professor Eros Lazzerini Denchi and Agnel Sfeir from New York University School of Medicine jointly organized the study. They said, "We have discovered the mechanism by which this mutation causes oncogenes to rage, and this mechanism is a sign that people really have tumors."

　　a puzzling discovery

　　Researchers have studied a gene mutation that codes for the POT1 protein. Under normal circumstances, this protein forms a protective "cap" structure along the ends of the chromosomes (telomeres) to prevent cellular machinery from accidentally damaging the DNA and harmful mutations.

　　POT1 is very important to cells. Cells lacking functional POT1 will die instead of passing on the POT1 mutation. The stress of these cells will result in the activation of the ATR enzyme, which initiates the death of the programmed cells.

　　In this context, scientists have discovered periodic mutations affecting the POT1 protein in several human cancers.

　　"Somehow, these cells (lack of functional POT1) have found a way to survive and proliferate," said LazzeriniDenchi. "We think that if we can understand how this happens, maybe we can find a way to kill these cells. ".

　　One slap doesn't sound

　　Researchers have discovered through mouse models that when POT1 mutations are accompanied by p53 gene mutations, cancer will appear.

　　LazzeriniDenchi said, "These cells no longer have a mechanism for spontaneous death, and the mouse has developed a severely aggressive thymic lymphoma."

　　P53, a well-known tumor suppressor gene, is a cunning accomplice. When the mutation occurs, p53 ignores the protective cell death response initiated by ATR. Therefore, without the protective "cap" structure formed by POT1, chromosomes will gather together and DNA recombination will occur, which will drive more mutation accumulation. These mutant cells continue to proliferate and form aggressive tumors.

　　These findings made the whole team think about a new strategy to kill tumors.

　　Scientists know that if all cells, including cancer cells, lose ATR, they will die. Because tumors with mutant POT1 low-express ATR, researchers are thinking that drugs that remove the remaining ATR may kill the tumor without damaging healthy cells. Lazzerini Denchi said, "This study shows that by thinking about the most basic biological problems, we will be able to find new ways to treat cancer."

　　Researchers plan to continue to review this new treatment in future studies.