An oncosuppressor can become an oncogene
There is a dark side to the indicator of a good cancer prognosis
Julia Korowski, XXII CENTURY, based on the materials of The University of Manchester: Good indicator of cancer prognosis turned on its head by new research
A molecule called p21WAF1/Cip1 (abbreviated p21) is often found in combination with the so-called tumor suppressor protein p53. High expression of p21 was considered a good sign for cancer patients – it meant that p53 would slow down the development of the tumor. A new study by an international group of scientists published in the journal Nature Cell Biology (Galanos et al., Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing), showed that not everything is so simple.
The molecular structure of p21. This protein has been described by several groups of researchers independently of each other, therefore it has several names: WAF1 (wild-type p53 activated fragment 1), CIP1 (CDK2 interacting protein 1), SDI1 (senescent derived inhibitor 1) and mda-6 (melanoma differentiation associated gene).
It turned out that if the p53 protein is not enough, p21 significantly accelerates tumor growth. "A few years ago, it was believed that sunbathing was one of the best ways to maintain health, and then we realized that too much sun is harmful. It's a similar story with this protein," says Professor Paul Townsend, one of the authors of the study. – If the wild-type p53 is lost, excessive production of p21 is not worth rejoicing. This protein, which was previously considered harmless, has a dark side."
The discovery was the result of five years of p21 research, during which scientists tried to develop drugs that increase the protein content and suppress the development of tumors. The members of the scientific group noticed that in tumors devoid of p53, an increase in the amount of p21 led to aggressive growth. It turned out that the protein p21 disrupts the mechanisms of DNA synthesis, this process is called replicative stress. It leads to genome instability, which is the "calling card" of cancer.
"Now we know that when p21 is produced without control from p53, it shows dangerous symptoms of cell division characteristic of aggressive tumors. Although this contradicts everything that has been known up to this point, there is hope that our discovery will help develop new ways to treat cancer in the future," Townsend sums up.
p21WAF1 is an intracellular protein inhibitor of cyclin–dependent kinase 1A, plays a critical role in the cellular response to DNA damage. The exact role of the protein in the origin and development of tumors is unknown. Studies show that in some types of tumors, the loss of p21 is a sign of poor chances of survival. However, there are situations when an increased concentration of p21 in cells is associated with the aggressiveness of the tumor.
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12.07.2016